Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Typ-2-Diabetes und Adipositas Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Häufige urologisch-sexualmedizinische Themen in der Praxis sind das Thema des MMW-Webinars am 5. Juni von 17.30 bis 19 Uhr. Konkret geht es um die Frage, wann bei Harnwegsinfektionen auf Antibiotika verzichtet werden kann, und um ein Update zur Therapie von Libido- und Potenzstörungen des Mannes. Der dritte Vortrag behandelt sexuell übertragbare Krankheiten. Stellen Sie Ihre Fragen an die Experten und sammeln Sie 2 CME-Punkte. Jetzt gleich anmelden!
Erweiterte Suche
Anmelden
nach oben
Clinical Pharmacokinetics
Erschienen in: Clinical Pharmacokinetics 2/2000

01.02.2000 | Review Article

Effects of the Antifungal Agents on Oxidative Drug Metabolism

Clinical Relevance

verfasst von: Karthik Venkatakrishnan, Lisa L. von Moltke, Dr David J. Greenblatt

Erschienen in: Clinical Pharmacokinetics | Ausgabe 2/2000

Einloggen, um Zugang zu erhalten

Abstract

This article reviews the metabolic pharmacokinetic drug-drug interactions with the systemic antifungal agents: the azoles ketoconazole, miconazole, itraconazole and fluconazole, the allylamine terbinafine and the sulfonamide sulfamethoxazole. The majority of these interactions are metabolic and are caused by inhibition of cytochrome P450 (CYP)-mediated hepatic and/or small intestinal metabolism of coadministered drugs.
Human liver microsomal studies in vitro, clinical case reports and controlled pharmacokinetic interaction studies in patients or healthy volunteers are reviewed. A brief overview of the CYP system and the contrasting effects of the antifungal agents on the different human drug-metabolising CYP isoforms is followed by discussion of the role of P-glycoprotein in presystemic extraction and the modulation of its function by the antifungal agents. Methods used for in vitro drug interaction studies and in vitro—in vivo scaling are then discussed, with specific emphasis on the azole antifungals.
Ketoconazole and itraconazole are potent inhibitors of the major drugmetabolising CYP isoform in humans, CYP3A4. Coadministration of these drugs with CYP3A substrates such as cyclosporin, tacrolimus, alprazolam, triazolam, midazolam, nifedipine, felodipine, simvastatin, lovastatin, vincristine, terfenadine or astemizole can result in clinically significant drug interactions, some of which can be life-threatening. The interactions of ketoconazole with cyclosporin and tacrolimus have been applied for therapeutic purposes to allow a lower dosage and cost of the immunosuppressant and a reduced risk of fungal infections. The potency of fluconazole as a CYP3A4 inhibitor is much lower. Thus, clinical interactions of CYP3A substrates with this azole derivative are of lesser magnitude, and are generally observed only with fluconazole dosages of ≥200 mg/day.
Fluconazole, miconazole and sulfamethoxazole are potent inhibitors of CYP2C9. Coadministration of phenytoin, warfarin, sulfamethoxazole and losartan with fluconazole results in clinically significant drug interactions. Fluconazole is a potent inhibitor of CYP2C19 in vitro, although the clinical significance of this has not been investigated. No clinically significant drug interactions have been predicted or documented between the azoles and drugs that are primarily metabolised by CYP 1A2, 2D6 or 2E1.
Terbinafine is a potent inhibitor of CYP2D6 and may cause clinically significant interactions with coadministered substrates of this isoform, such as nortriptyline, desipramine, perphenazine, metoprolol, encainide and propafenone. On the basis of the existing in vitro and in vivo data, drug interactions of terbinafine with substrates of other CYP isoforms are unlikely.
Literatur
1.
Como JA, Dismukes WE. Oral azole drugs as systemic antifungal therapy. N Engl J Med 1994; 330: 263–72.CrossRefPubMed
2.
Kauffman CA, Carver PL, Antifungal agents in the 1990s: current status and future developments. Drugs 1997; 53: 539–49.CrossRefPubMed
3.
Bräutigam M, Nolting S, Schopf RE, et al. Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. BMJ 1995; 311: 919–22.CrossRefPubMed
4.
Backer MD, Keyser PD, Vroey CD, et al. A 12-week treatment for dermatophyte toe onychomycosis: terbinafine 250 mg/day vs. itraconazole 200 mg/day - a double-blind comparative trial. Br J Dermatol 1996; 134 Suppl. 46: 16–7.
5.
Evans EGV, Sigurgeirsson B, Double blind, randomised study of continuous terbinafine compared with intermittent itraconazole in the treatment of toenail onychomycosis. BMJ 1999; 318: 1031–5.CrossRefPubMed
6.
Albengres E, Le Louët H, Tillement J-P. Systemic antifungal agents: drug interactions of clinical significance. Drug Saf 1998; 18: 83–97.CrossRefPubMed
7.
Lomaestro BM, Piatek MA, Update on drug interactions with azole antifungal agents. Ann Pharmacother 1998; 32: 915–28.CrossRefPubMed
8.
Guengerich FP. Comparisons of catalytic selectivity of cytochrome P450 subfamily enzymes from different species. Chem Biol Interact 1997; 106: 161–82.CrossRefPubMed
9.
Eagling VA, Tjia JF, Back DJ. Differential selectivity of cytochrome P450 inhibitors against probe substrates in human and rat liver microsomes. Br J Clin Pharmacol 1998; 45: 107–14.CrossRefPubMed
10.
Abdel-Rahman SM, Marcucci K, Böge T, et al. Potent inhibition of cytochrome P-450 2D6-mediated dextromethorphan O-demethyl-ation by terbinafine. Drug Metab Dispos 1999; 27: 770–5.PubMed
11.
Abdel-Rahman SM, Gotschall RR, Kauffman RE, et al. Investigation of terbinafine as a CYP2D6 inhibitor in vivo. Clin Pharmacol Ther 1999; 65: 465–72.CrossRefPubMed
12.
Hajek KK, Cook NI, Novak RF. Mechanism of inhibition of micro-somal drug metabolism by imidazole. J Pharmacol Exp Ther 1982; 223: 97–104.PubMed
13.
Schuster I. The interaction of representative members from two classes of antimycotics — the azoles and the allylamines — with cytochromes P-450 in steroidogenic tissues and liver. Xenobiotica 1985; 15: 529–46.CrossRefPubMed
14.
Shimada T, Yamazaki H, Mimura M, et al. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 1994; 270: 414–23.PubMed
15.
Wrighton SA, Ring BJ. Inhibition of human CYP3A catalyzed 1′-hydroxy midazolam formation by ketoconazole, nifedipine, eryth-romycin, cimetidine, and nizatidine. Pharm Res 1994; 11: 921–4.CrossRefPubMed
16.
Hargreaves JA, Jezequel S, Houston JB. Effect of azole antifungals on human microsomal metabolism of diclofenac and midazolam. Br J Clin Pharmacol 1994; 38: 175P.
17.
Lampen A, Christians U, Guengerich FP, et al. Metabolism of the immunosuppressant tacrolimus in the small intestine: cytochrome P450, drug interactions, and interindividual variability. Drug Metab Dispos 1995; 23: 1315–23.PubMed
18.
Gentile DM, Tomlinson ES, Maggs JL, et al. Dexamethasone metabolism by human liver in vitro. Metabolite identification and inhibition of 6-hydroxylation. J Pharmacol Exp Ther 1996; 277: 105–12.
19.
Christians U, Schmidt G, Bader A, et al. Identification of drugs inhibiting the in vitro metabolism of tacrolimus by human liver microsomes. Br J Clin Pharmacol 1996; 41: 187–90.CrossRefPubMed
20.
Gibbs MA, Thummel KE, Shen DD, et al. Inhibition of cytochrome P-450 3A (CYP3A) in human intestinal and liver microsomes: comparison of Ki values and impact of CYP3A5 expression. Drug Metab Dispos 1999; 27: 180–7.PubMed
21.
Omar G, Whiting PH, Hawksworth GM, et al. Ketoconazole and fluconazole inhibition of the metabolism of cyclosporin A by human liver in vitro. Ther Drug Monit 1997; 19: 436–45.CrossRefPubMed
22.
Baune B, Furlan V, Taburet AM, et al. Effect of selected antimalarial drugs and inhibitors of cytochrome P-450 3A4 on halofantrine metabolism by human liver microsomes. Drug Metab Dispos 1999; 27: 565–8.PubMed
23.
Pichard L, Fabre I, Fabre G, et al. Cyclosporin A drug interactions: screening for inducers and inhibitors of cytochrome P-450 (cyclosporin A oxidase) in primary cultures of human hepatocytes and liver microsomes. Drug Metab Dispos 1990; 18: 595–606.PubMed
24.
Back DJ, Tjia JF. Comparative effects of the antimycotic drugs ketoconazole. fluconazole. itraconazole and terbinafine on the metabolism of cyclosporin by human liver microsomes. Br J Clin Pharmacol 1991; 32: 624–6.
25.
Lavrijsen K, Van Houdt J, Meuldermans W, et al. The interaction of ketoconazole. itraconazole and erythromycin with the in vitro metabolism of antihistamines in human liver microsomes. Allergy 1993; 48: 34.
26.
Zhou-Pan XR, Sérée E, Zhou X-J, et al. Involvement of cytochrome P450 3A in vinblastine metabolism: drug interactions. Cancer Res 1993; 53: 5121–6.PubMed
27.
von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibitors of alprazolam metabolism in vitro: effect of serotonin-reuptake-inhibitor antidepressants, ketoconazole and quinidine. Br J Clin Pharmacol 1994; 38: 23–31.CrossRef
28.
von Moltke LL, Greenblatt DJ, Cotreau-Bibbo MM, et al. Inhibition of desipramine hydroxylation in vitro by serotonin-reuptake-inhibitor anti depress ants, and by quinidine and ketoconazole: a model system to predict drug interactions in vivo. J Pharmacol Exp Ther 1994; 268: 1278–83.
29.
von Moltke LL, Greenblatt DJ, Duan SX, et al. In vitro prediction of the terfenadine-ketoconazole pharmacokinetic interaction. J Clin Pharmacol 1994; 34: 1222–7.
30.
von Moltke LL, Greenblatt DJ, Harmatz JS, et al. Triazolam biotransformation by human liver microsomes in vitro: effects of metabolic inhibitors, and clinical confirmation of a predicted interaction with ketoconazole. J Pharmacol Exp Ther 1996; 276: 370–9.
31.
von Moltke LL, Greenblatt DJ, Schmider J, et al. Midazolam hydroxylation by human liver microsomes in vitro: inhibition by fluoxetine. norfluoxetine. and by azole antifungal agents. J Clin Pharmacol 1996; 36: 783–91.
32.
von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of terfenadine metabolism in vitro by azole antifungal agents and by selective serotonin-reuptake inhibitor antidepressants: relation to pharmacokinetic interactions in vivo. J Clin Psychopharmacol 1996; 16: 104–12.CrossRef
33.
von Moltke LL, Greenblatt DJ, Duan SX, et al. Human cytochromes mediating /V-demethylation of fluoxetine in vitro. Psychopharma-cology 1997; 132: 402–7.CrossRef
34.
Jurima-Romet M, Crawford K, Cyr T, et al. Terfenadine metabolism in human liver: in vitro inhibition by macrolide antibiotics and azole antifungals. Drug Metab Dispos 1994; 22: 849–57.PubMed
35.
Mitra AK, Thummel KE, Kalhorn TF, et al. Inhibition of sulfamethoxazole hydroxylamine formation by fluconazole in human liver microsomes and healthy volunteers. Clin Pharmacol Ther 1996; 59: 332–40.CrossRefPubMed
36.
Iatsimirskaia E, Tulebaev S, Storozhuk E, et al. Metabolism of rifabutin in human enterocyte and liver microsomes: kinetic parameters, identification of enzyme systems, and drug interactions with macrolides and antifungal agents. Clin Pharmacol Ther 1997; 61: 554–62.CrossRefPubMed
37.
Nakasa H, Komiya M, Ohmori S, et al. Characterization of human liver microsomal cytochrome P450 involved in the reductive metabolism of zonisamide. Mol Pharmacol 1993; 44: 216–21.PubMed
38.
Nielsen TL, Rasmussen BB, Flinois J-P, et al. In vitro metabolism of quinidine: the (3S)-3-hydroxylation of quinidine is a specific marker reaction for cytochrome P-4503 A4 activity in human liver microsomes. J Pharmacol Exp Ther 1999; 289: 31–7.PubMed
39.
Bourrié M, Meunier V, Berger Y, et al. Cytochrome P450 isoform inhibitors as a tool for the investigation of metabolic reactions catalyzed by human liver microsomes. J Pharmacol Exp Ther 1996; 277: 321–32.PubMed
40.
Kunze KL, Wienkers LC, Thummel KE, et al. Warfarin-fluconazole I: inhibition of human cytochrome P450-dependent metabolism of warfarin by fluconazole: in vitro studies. Drug Metab Dispos 1996; 24: 414–21.PubMed
41.
Fitzsimmons ME, Collins JM. Selective biotransformation of the human immunodeficiency virus protease inhibitor saquinavir by human small-intestinal cytochrome P4503A4. Drug Metab Dispos 1997; 25: 256–66.PubMed
42.
Paine MF, Schmiedlin-Ren P, Watkins PB. Cytochrome P-450 1A1 expression in human small bowel: interindividual variation and inhibition by ketoconazole. Drug Metab Dispos 1999; 27: 360–4.PubMed
43.
Segel IH. Enzyme Kinetics. New York: John Wiley and Sons, 1975.
44.
Maurice M, Pichard L, Daujat M, et al. Effects of imidazole derivatives on cytochromes P450 from human hepatocytes in primary culture. FASEB J 1992; 6: 752–8.PubMed
45.
von Moltke LL, Greenblatt DJ, Duan SX, et al. Phenacetin O-deethylation by human liver microsomes in vitro: inhibition by chemical probes, SSRI antidepressants, nefazodone, and venlafaxine. Psychopharmacology 1996; 128: 398–407.CrossRef
46.
Ono S, Hatanaka T, Hotta H, et al. Specificity of substrate and inhibitor probes for cytochrome P450s: evaluation of in vitro metabolism using cDNA-expressed human P450s and human liver microsomes. Xenobiotica 1996; 26: 681–93.CrossRefPubMed
47.
Zhang Q-Y, Dunbar D, Ostrowska A, et al. Characterization of human small intestinal cytochromes P-450. Drug Metab Dispos 1999; 27: 804–9.PubMed
48.
Eugster H-P, Sengstag C, Meyer UA, et al. Constitutive and inducible expression of human cytochrome P4501A1 in yeast Saccha-romyces cerevisiae: an alternative enzyme source for in vitro studies. Biochem Biophys Res Commun 1990; 172: 737–44.CrossRefPubMed
49.
Pasanen M, Taskinen T, Iscan M, et al. Inhibition of human hepatic and placental xenobiotic monooxygenases by imidazole antimycotics. Biochem Pharmacol 1988; 37: 3861–6.CrossRefPubMed
50.
Draper AJ, Madan A, Parkinson A. Inhibition of coumarin 7-hy-droxylase activity in human liver microsomes. Arch Biochem Biophys 1997; 341: 47–61.CrossRefPubMed
51.
Code EL, Crespi CL, Penman BW, et al. Human cytochrome P4502B6. Interindividual hepatic expression, substrate specificity, and role in procarcinogen activation. Drug Metab Dispos 1997; 25: 985–93.
52.
Ekins S, Vandenbranden M, Ring BJ, et al. Further characterization of the expression in liver and catalytic activity of CYP2B6. J Pharmacol Exp Ther 1998; 286: 1253–9.PubMed
53.
Stresser DM, Kupfer D. Monospecific antipeptide antibody to cytochrome P-450 2B6. Drug Metab Dispos 1999; 27: 517–25.PubMed
54.
Roy P, Yu LJ, Crespi CL, et al. Development of a substrate-activity based approach to identify the major human liver P-450 catalysts of cyclophosphamide and ifosfamide activation based on cDNA-expressed activities and liver microsomal P-450 profiles. Drug Metab Dispos 1999; 27: 655–66.PubMed
55.
Erickson DA, Riska PS, Hattox SE, et al. Nevirapine hydroxylation, an in vitro probe for the simultaneous determination of CYP3A and CYP2B6 activity in human liver microsomes. ISSX Proc 1997; 12: 49.
56.
Heyn H, White RB, Stevens JC. Catalytic role of cytochrome P4502B6 in the /V-demethylation of S-mephenytoin. Drug Metab Dispos 1996; 24: 948–54.PubMed
57.
Ko JW, Desta Z, Flockhart DA. Human N-demethylation of S-mephenytoin by cytochrome P450s 2C9 and 2B6. Drug Metab Dispos 1998; 26: 775–8.PubMed
58.
Chang TKH. Differential activation of cyclophosphamide and ifosphamide by cytochrome P-450 2B and 3A in human liver microsomes. Cancer Res 1993; 53: 5629–37.PubMed
59.
Inoue K, Yamazaki H, Imiya K, et al. Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics 1997; 7: 103–13.CrossRefPubMed
60.
Lasker JM, Wester MR, Aramsombatdee E, et al. Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hy-droxylations. Arch Biochem Biophys 1998; 353: 16–28.CrossRefPubMed
61.
Crespi CL. Xenobiotic-metabolizing human cells as tools for pharmacological and toxicological research. Adv Drug Res 1995; 26: 179–235.CrossRef
62.
Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Relative quantities of catalytically active CYP 2C9 and 2C19 in human liver microsomes: application of the relative activity factor approach. J Pharm Sci 1998; 87: 845–53.CrossRefPubMed
63.
Back DJ, Stevenson P, Tjia JF. Comparative effects of two anti-mycotic agents, ketoconazole and terbinafine on the metabolism of tolbutamide, ethinyloestradiol, cyclosporin and ethoxycou-marin by human liver microsomes in vitro. Br J Clin Pharmacol 1989; 28: 166–70.CrossRefPubMed
64.
O’Reilly RA, Goulart DA, Kunze KL, et al. Mechanisms of the stereo selective interaction between miconazole and racemic warfarin in human subjects. Clin Pharmacol Ther 1992; 51: 656–67.CrossRefPubMed
65.
O’Reilly RA. Stereo selective interaction of trimethoprim-sul-famethoxazole with the separated enantiomorphs of racemic warfarin in man. N England J Med 1980; 302: 33–5.CrossRef
66.
Back DJ, Tjia JF, Karbwang J, et al. In vitro inhibition studies of tolbutamide hydroxylase activity of human liver microsomes by azoles, sulphonamides and quinolines. Br J Clin Pharmacol 1988; 26: 23–9.CrossRefPubMed
67.
Krishnaiah YSR, Satyanarayana S, Visweswaram D. Interaction between tolbutamide and ketoconazole in healthy subjects. Br J Clin Pharmacol 1994; 37: 205–7.CrossRefPubMed
68.
Gill HJ, Maggs JL, Madden S, et al. The effect of fluconazole and ketoconazole on the metabolism of sulfamethoxazole. Br J Clin Pharmacol 1996; 42: 347–53.CrossRefPubMed
69.
Touchette MA, Chandrasekar PH, Milad MA, et al. Contrasting effects of fluconazole and ketoconazole on phenytoin and testosterone disposition in man. Br J Clin Pharmacol 1992; 34: 75–8.CrossRefPubMed
70.
Flockhart DA. Drug interactions and the cytochrome P450 system: the role of cytochrome P450 2C19. Clin Pharmacokinet 1995; 29 Suppl. 1: 45–52.CrossRefPubMed
71.
Hall SD, Guengerich FP, Branch RA, et al. Characterization and inhibition of mephenytoin 4-hydroxylase activity in human liver microsomes. J Pharmacol Exp Ther 1987; 240: 216–22.PubMed
72.
Atiba JO, Blaschke TF, Wilkinson GR. Effects of ketoconazole on the polymorphic 4-hydroxylations of S-mephenytoin and debrisoquine. Br J Clin Pharmacol 1989; 28: 161–5.CrossRefPubMed
73.
Böttiger Y, Tybring G, Götharson E, et al. Inhibition of the sulfoxida-tion of omeprazole by ketoconazole in poor and extensive meta-bolizers of S-mephenytoin. Clin Pharmacol Ther 1997; 62: 384–91.CrossRefPubMed
74.
Wienkers LC, Wurden CJ, Storch E, et al. Formation of (R)-8-hydroxywarfarin in human liver microsomes: a new metabolic marker for the (S)-mephenytoin hydroxylase, P4502C19. Drug Metab Dispos 1996; 24: 610–4.PubMed
75.
Jamis-Dow CA, Klecker RW, Katki AG, et al. Metabolism of taxol by human and rat liver in vitro: a screen for drug interactions and interspecies differences. Cancer Chemother Pharmacol 1995; 36: 107–14.CrossRefPubMed
76.
Jamis-Dow CA, Pearl ML, Watkins PB, et al. Predicting drug interactions in vivo from experiments in vitro: human studies with paclitaxel and ketoconazole. Am J Clin Oncol 1997; 20: 592–9.CrossRefPubMed
77.
Fromm MF, Kroemer HK, Eichelbaum M. Impact of P450 genetic polymorphism on the first-pass extraction of cardiovascular and neuroactive drugs. Adv Drug Deliv Rev 1997; 27: 171–99.CrossRefPubMed
78.
Leeder JS, Gotschall RR, Gaedigk A, et al. CYP2D6 phenotype-genotype discordance and potential new drug-drug interactions. Clin Pharmacol Ther 1998; 63: 216.
79.
van der Kuy P-HM, Hooymans PM, Verkaaik AJB. Nortriptyline intoxication induced by terbinafine. BMJ 1998; 316: 441.CrossRefPubMed
80.
Newton DJ, Wang RW, Lu AYH. Cytochrome P450 inhibitors: evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 1995; 23: 154–8.PubMed
81.
Tassaneeyakul W, Birkett DJ, Miners JO. Inhibition of human hepatic cytochrome P4502E1 by azole antifungals. CNS-active drugs and nonsteroidal antiinflammatory agents. Xenobiotica 1998; 28: 293–301.
82.
Baldwin SJ, Bloomer JC, Smith GJ, et al. Ketoconazole and sulphaphenazole as the respective selective inhibitors of P4503 A and 2C9. Xenobiotica 1995; 25: 261–70.CrossRefPubMed
83.
von Moltke LL, Greenblatt DJ, Duan SX, et al. Inhibition of triazolam hydroxylation by ketoconazole. itraconazole, hydroxyitra-conazole and fluconazole in vitro. Pharm Pharmacol Commun 1998; 4: 443–5.
84.
Heykants J, Michiels M, Meuldermans W, et al. The pharmacokinetics of itraconazole in animals and man: an overview. In Fromtling R, editor. Recent trends in the discovery, development and evaluation of antifungal agents. Barcelona: J.R. Prous Science Publishers, 1987: 223–49.
85.
Heykants J, Van Peer A, Lavrijsen K, et al. Pharmacokinetics of oral antifungals and their clinical implications. Br J Clin Pract 1990; 44 (9 Suppl.): 50–6.
86.
Morita K, Konishi H, Shimakawa H. Fluconazole: a potent inhibitor of cytochrome P-450-dependent drug metabolism in mice and humans in vivo. Comparative study with ketoconazole. Chem Pharm Bull 1992; 40: 1247–51.CrossRef
87.
Gibbs MA, Kunze KL, Howald WN, et al. Effect of inhibitor depletion on inhibitor potency: tight binding inhibition of CYP3A by clotrimazole. Drug Metab Dispos 1999; 27: 596–9.PubMed
88.
Wacher VJ, Wu C-Y, Benet LZ. Overlapping substrate specificities and tissue distribution of cytochrome P450 3A and P-glycoprotein: implications for drug delivery and activity in cancer chemotherapy. Mol Carcinog 1995; 13: 129–34.CrossRefPubMed
89.
Watkins PB. The barrier function of CYP3A4 and P-glycoprotein in the small bowel. Adv Drug Deliv Rev 1997; 27: 161–70.CrossRefPubMed
90.
Lown KS, Mayo RR, Leichtman AB, et al. Role of intestinal P-glycoprotein (mdrl) in interpatient variation in the oral bioavailability of cyclosporine. Clin Pharmacol Ther 1997; 62: 248–60.CrossRefPubMed
91.
Schuetz EG, Beck WT, Schuetz JD. Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells. Mol Pharmacol 1996; 49: 311–8.PubMed
92.
Schinkel AH, Smit JJM, van Tellingen O, et al. Disruption of the mouse mdrla p-glycoprotein gene leads to a deficiency in the blood-brain barrier and to increased sensitivity to drugs. Cell 1994; 77: 491–502.CrossRefPubMed
93.
Schinkel AH, Wagenaar E, van Deemter L, et al. Absence of the mdrla p-glycoprotein in mice affects tissue distribution and pharmacokinetics of dexamethasone, digoxin, and cyclosporin A. J Clin Invest 1995; 96: 1698–705.CrossRefPubMed
94.
Schinkel AH. Pharmacological insights from P-glycoprotein knockout mice. Int J Clin Pharmacol Ther 1998; 36: 9–13.PubMed
95.
Schuetz EG, Schinkel AH, Relling MV, et al. P-glycoprotein: a major determinant of rifampicin-inducible expression of cytochrome P4503A in mice and humans. Proc Natl Acad Sci USA 1996; 93: 4001–5.CrossRefPubMed
96.
Kim RB, Wandel C, Leake B, et al. Interrelationship between substrates and inhibitors of human CYP3 A and P-glycoprotein. Pharm Res 1999; 16: 408–14.CrossRefPubMed
97.
Perloff MD, von Moltke LL, Cotreau MM, et al. Unchanged CYP 3 A expression and metabolism of midazolam, triazolam, and dexamethasone in mdr (−/−) mouse liver microsomes. Biochem Pharmacol 1999; 57: 1227–32.CrossRefPubMed
98.
Takano M, Hasegawa R, Fukuda T, et al. Interaction with P-glycoprotein and transport of erythromycin, midazolam and ketoconazole in Caco-2 cells. Eur J Pharmacol 1998; 358: 289–94.CrossRefPubMed
99.
von Moltke LL, Granda BW, Grassi JM, et al. Multiple site interaction of triazolam and ketoconazole in mice: role of P-glycoprotein [abstract]. Clin Pharmacol Ther 1999; 65: 143.
100.
Siegsmund MJ, Cardarelli C, Aksentijevich I, et al. Ketoconazole effectively reverses multidrug resistance in highly resistant KB cells. J Urol 1994; 151: 485–91.PubMed
101.
Woodland C, Ito S, Koren G. A model for the prediction of digoxindrug interactions at the renal tubular cell level. Ther Drug Monit 1998; 20: 134–8.CrossRefPubMed
102.
Döppenschmitt S, Spahn-Langguth H. Regårdh CG. Radioligandbinding assay employing P-glycoprotein-overexpressing cells: testing drug affinities to the secretory intestinal multidrug transporter. Pharm Res 1998; 15: 1001–6.
103.
Zhang Y, Hsieh Y, Izumi T, et al. Effects of ketoconazole on the intestinal metabolism, transport and oral bioavail ability of K02, a novel vinylsulfone peptidomimetic cysteine protease inhibitor and a P450 3A, P-glycoprotein dual substrate, in male Sprague-Dawley rats. J Pharmacol Exp Ther 1998; 287: 246–52.PubMed
104.
Yumoto R, Murakami T, Nakamoto Y, et al. Transport of rhodamine 123. a P-glycoprotein substrate, across rat intestine and Caco-2 cell monolayers in the presence of cytochrome P-450 3A-related compounds. J Pharmacol Exp Ther 1999; 289: 149–55.
105.
Miyama T, Takanaga H, Matsuo H, et al. P-glycoprotein-mediated transport of itraconazole across the blood-brain-barrier. Anti-microb Agents Chemother 1998; 42: 1738–44.
106.
Gupta S, Kim J, Gollapudi S. Reversal of daunorubicin resistance in P388/ADR cells by itraconazole. J Clin Invest 1991; 87: 1467–9.CrossRefPubMed
107.
Kurosawa M, Okabe M, Hara N.etal. Reversal effect of itraconazole on adriamycin and etoposide resistance in human leukemia cells. Ann Hematol 1996; 72: 17–21.CrossRefPubMed
108.
Böhme A, Ganser A, Hoelzer D. Aggravation of vincristine-induced neurotoxicity by itraconazole in the treatment of adult ALL. Ann Hematol 1995; 71: 311–2.CrossRefPubMed
109.
Jalava KM, Partanen J, Neuvonen PJ. Itraconazole decreases renal clearance of digoxin. Ther Drug Monit 1997; 19: 609–13.CrossRefPubMed
110.
Tarral A, Francheteau P, Guerret M. Effect of terbinafine on the pharmacokinetics of digoxin in healthy volunteers. Pharmacotherapy 1997; 17: 791–5.PubMed
111.
von Moltke LL, Greenblatt DJ, Schmider J, et al. Metabolism of drugs by cytochrome P450 3A isoforms: implications for drug interactions in psychopharmacology. Clin Pharmacokinet 1995; 29 Suppl. 1: 33–43.CrossRef
112.
Greenblatt DJ, von Moltke LL. Can in vitro models predict drug interactions in vivo? A review of methods, problems, and successes. In: Hori W, editor. Drug-drug interactions: analyzing in vitro-in vivo correlations. Southboro (MA): International Business Communications, 1997: pp 2.2.1–28
113.
Bertz RJ, Granneman GR. Use of in vitro and in vivo data to estimate the likelihood of metabolic pharmacokinetic interactions. Clin Pharmacokinet 1997; 32: 210–58.CrossRefPubMed
114.
von Moltke LL, Greenblatt DJ, Schmider J, et al. In vitro approaches to predicting drug interactions in vivo. Biochem Pharmacol 1998; 55: 113–22.CrossRef
115.
Witherow LE, Houston JB. Sigmoidal kinetics of CYP3 A substrates: an approach for scaling dextromethorphan metabolism in hepatic microsomes and isolated hepatocytes to predict in vivo clearance in the rat. J Pharmacol Exp Ther 1999; 290: 58–65.PubMed
116.
Schmider J, Greenblatt DJ, von Moltke LL, et al. N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms. and effect of metabolic inhibitors. J Pharmacol Exp Ther 1995; 275: 592–7.
117.
Obach RS. The importance of nonspecific binding in in vitro matrices, its impact on enzyme kinetic studies of drug metabolism reactions, and implications for in vitro-in vivo correlations. Drug Metab Dispos 1996; 24: 1047–9.PubMed
118.
Obach RS. Nonspecific binding to microsomes: impact on scale-up of in vitro intrinsic clearance to hepatic clearance as assessed through examination of warfarin, imipramine. and propranolol. Drug Metab Dispos 1997; 25: 1359–69.
119.
Obach RS, Baxter JG, Liston TE, et al. The prediction of human pharmacokinetic parameters from preclinical and in vitro metabolism data. J Pharmacol Exp Ther 1997; 283: 46–58.PubMed
120.
Borin MT, Cox SR, Herman BD, et al. Effect of fluconazole on the steady-state pharmacokinetics of delavirdine in human immunodeficiency virus-positive patients. Antimicrob Agents Chemother 1997; 41: 1892–7.PubMed
121.
Knupp CA, Brater DC, Relue J, et al. Pharmacokinetics of didanos-ine and ketoconazole after co-administration to patients séropositive for the human immunodeficiency virus. J Clin Pharmacol 1993; 33: 912–7.PubMed
122.
De Wit S, Debier M, De Smet M, et al. Effect of fluconazole on indinavir pharmacokinetics in human immunodeficiencyvirus-infected patients. Antimicrob Agents Chemother 1998; 42: 223–7.PubMed
123.
Kaukonen K-M, Olkkola KT, Neuvonen PJ. Fluconazole but not itraconazole decreases the metabolism of losartan to E-3174. Eur J Clin Pharmacol 1998; 53: 445–9.CrossRefPubMed
124.
Cobb MN, Desai J, Brown LS, et al. The effect of fluconazole on the clinical pharmacokinetics of methadone. Clin Pharmacol Ther 1998; 63: 655–62.CrossRefPubMed
125.
Ahonen J, Olkkola KT, Neuvonen PJ. Effect of route of administration of fluconazole on the interaction between fluconazole and midazolam. Eur J Clin Pharmacol 1997; 51: 415–9.CrossRefPubMed
126.
Blum RA, Wilton JH, Hilligoss DM, et al. Effect of fluconazole on the disposition of phenytoin. Clin Pharmacol Ther 1991; 49: 420–5.CrossRefPubMed
127.
Varhe A, Olkkola KT, Neuvonen PJ. Fluconazole. but not terbinafine. enhances the effects of triazolam by inhibiting its metabolism. Br J Clin Pharmacol 1996; 41: 319–23.
128.
Varhe A, Olkkola KT, Neuvonen PJ. Effect of fluconazole dose on the extent of fluconazole-triazolam interaction. Br J Clin Pharmacol 1996; 42: 465–70.CrossRefPubMed
129.
Black DJ, Kunze KL, Wienkers LC, et al. Warfarin-fluconazole II: a metabolically based drug interaction: in vivo studies. Drug Metab Dispos 1996; 24: 422–8.PubMed
130.
Sahai J, Gallicano K, Pakuts A, et al. Effect of fluconazole on zidovudine pharmacokinetics in patients infected with human immunodeficiency virus. J Infect Dis 1994; 169: 1103–7.CrossRefPubMed
131.
Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Kinetic and dynamic interaction study of zolpidem with ketoconazole. itraconazole. and fluconazole. Clin Pharmacol Ther 1998; 64: 661–71.CrossRef
132.
Kantola T, Kivistö KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics of atorvastatin. Clin Pharmacol Ther 1998; 64: 58–65.CrossRefPubMed
133.
Kivistö KT, Lamberg TS, Kantola T, et al. Plasma buspirone concentrations are greatly increased by erythromycin and itraconazole. Clin Pharmacol Ther 1997; 62: 348–54.CrossRefPubMed
134.
Kantola T, Kivistö KT, Neuvonen PJ. Effect of itraconazole on cerivastatin pharmacokinetics. Eur J Clin Pharmacol 1999; 54: 851–5.CrossRefPubMed
135.
Raaska K, Neuvonen PJ. Serum concentrations of clozapine and N-desmethylclozapine are unaffected by the potent CYP3A4 inhibitor itraconazole. Eur J Clin Pharmacol 1998; 54: 167–70.CrossRefPubMed
136.
Jalava K-M, Olkkola KT, Neuvonen PJ. Itraconazole greatly increases plasma concentrations and effects of felodipine. Clin Pharmacol Ther 1997; 61: 410–5.CrossRefPubMed
137.
Palkama VJ, Neuvonen PJ, Olkkola KT. The CYP3A4 inhibitor itraconazole has no effect on the pharmacokinetics of i.v. fentanyl. Br J Anaesth 1998; 81: 598–600.CrossRef
138.
Neuvonen PJ, Jalava K-M. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996; 60: 54–61.CrossRefPubMed
139.
Kivistö KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998; 46: 49–53.CrossRefPubMed
140.
Varis T, Kaukonen K-M, Kivistö KT, et al. Plasma concentrations and effects of oral methylprednisolone are considerably increased by itraconazole. Clin Pharmacol Ther 1998; 64: 363–8.CrossRefPubMed
141.
Olkkola KT, Backman JT, Neuvonen PJ, Midazolam should be avoided in patients receiving the systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994; 55: 481–5.CrossRefPubMed
142.
Ducharme MP, Slaughter RL, Warbasse LH, et al. Itraconazole and hydroxyitraconazole concentrations are reduced more than tenfold by phenytoin. Clin Pharmacol Ther 1995; 58: 617–24.CrossRefPubMed
143.
Kaukonen K-M, Olkkola KT, Neuvonen PJ. Itraconazole increases plasma concentrations of quinidine. Clin Pharmacol Ther 1997; 62: 510–7.CrossRefPubMed
144.
Neuvonen PJ, Kantola T, Kivistö KT. Simvastatin but not pravastatin is very susceptible to interaction with the CYP3A4 inhibitor itraconazole. Clin Pharmacol Ther 1998; 63: 332–41.CrossRefPubMed
145.
Varhe A, Olkkola KT, Neuvonen PJ. Oral triazolam is potentially hazardous to patients receiving systemic antimycotics ketoconazole or itraconazole. Clin Pharmacol Ther 1994; 56: 601–7.CrossRefPubMed
146.
Neuvonen PJ, Varhe A, Olkkola KT. The effect of ingestion time interval on the interaction between itraconazole and triazolam. Clin Pharmacol Ther 1996; 60: 326–31.CrossRefPubMed
147.
Luurila H, Kivistö KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zolpidem. Eur J Clin Pharmacol 1998; 54: 163–6.CrossRefPubMed
148.
Jalava K-M, Olkkola KT, Neuvonen PJ. Effect of itraconazole on the pharmacokinetics and pharmacodynamics of zopiclone. Eur J Clin Pharmacol 1996; 51: 331–4.CrossRefPubMed
149.
Daneshmend TK, Warnock DW, Ene MD, et al. Multiple dose pharmacokinetics of ketoconazole and their effects on antipyrine kinetics in man. J Antimicrob Chemother 1983; 12: 185–8.CrossRefPubMed
150.
Wahlländer A, Paumgartner G. Effect of ketoconazole and terbinafine on the pharmacokinetics of caffeine in healthy volunteers. Eur J Clin Pharmacol 1989; 37: 279–83.CrossRefPubMed
151.
Long CC, Hill SA, Thomas RC, et al. Effect of terbinafine on the pharmacokinetics of cyclosporin in humans. J Invest Dermatol 1994; 102: 740–3.CrossRefPubMed
152.
Robbins B, Chang C-T, Cramer JA, et al. Safe coadministration of terbinafine and terfenadine: a placebo-control led crossover study of pharmacokinetic and pharmacodynamic interactions in healthy volunteers. Clin Pharmacol Ther 1996; 59: 275–83.CrossRefPubMed
153.
Guerret M, Francheteau P, Hubert M. Evaluation of effects of terbinafine on single oral dose pharmacokinetics and anticoagulant actions of warfarin in healthy volunteers. Pharmacotherapy 1997; 17: 767–73.PubMed
154.
Yamano K, Yamamoto K, Kotaki H, et al. Quantitative prediction of metabolic inhibition of midazolam by itraconazole and ketoconazole in rats: implication of concentrative uptake of inhibitors into liver. Drug Metab Dispos 1999; 27: 395–402.PubMed
155.
Riley CM, James MO. Determination of ketoconazolein the plasma, liver, lung and adrenal of the rat by high-performance liquid chro-matography. J Chromatogr 1986; 377: 287–94.CrossRefPubMed
156.
Matthew D, Brennan B, Zomorodi K, et al. Disposition of azole antifungal agents. 1. Nonlinearities in ketoconazole clearance and binding in rat liver. Pharmaceut Res 1993; 10: 418–22.
157.
Ervine CM, Houston JB. Disposition of azole antifungal agents III: binding of fluconazole and other azoles in rat liver. Pharm Res 1994; 11: 961–5.CrossRefPubMed
158.
Ring BJ, Binkley SN, Roskos L, et al. Effect of fluoxetine, norfluoxetine. sertraline and desmethylsertraline on human CYP3A catalyzed l′-hydroxy midazolam formation in vitro. J Pharmacol Exp Ther 1995; 275: 1131–5.
159.
Kunze K, Trager W. Warfarin-fluconazole III: a rational approach to management of a metabolically based drug interaction. Drug Metab Dispos 1996; 24: 429–35.PubMed
160.
Ervine C, Matthew D, Brennan B, et al. Comparison of ketoconazole and fluconazole as cytochrome P450 inhibitors. Drug Metab Dispos 1996; 24: 211–5.PubMed
161.
Daneshmend TK, Warnock DW. Clinical pharmacokinetics of ketoconazole. Clin Pharmacokinet 1988; 14: 13–34.CrossRefPubMed
162.
Fahey JM, Pritchard GA, von Moltke LL, et al. The effects of ketoconazole on triazolam pharmacokinetics. pharmacodynamics and benzodiazepine receptor binding in mice. J Pharmacol Exp Ther 1998; 285: 271–6.
163.
Meyer JC, Burri C, Ruf P, et al. Factors affecting plasma levels of ketoconazole during long-term treatment. Dermatologica 1989; 178: 29–32.CrossRefPubMed
164.
Ahonen J, Olkkola K, Neuvonen P. Effect of itraconazole and terbinafine on the pharmacokinetics and pharmacodynamics of midazolam in healthy volunteers. Br J Clin Pharmacol 1995; 40: 270–2.PubMed
165.
Olkkola K, Ahonen J, Neuvonen P. The effect of the systemic anti-mycotics, itraconazole and fluconazole. on the pharmacokinetics and pharmacodynamics of intravenous and oral midazolam. Anesth Analg 1996; 82: 511–6.
166.
Brammer KW, Farrow PR, Faulkner JK. Pharmacokinetics and tissue penetration of fluconazole in humans. Rev Infect Dis 1990; 12: S318–S26.CrossRefPubMed
167.
Ripa S, Ferrante L, Prenna M. Pharmacokinetics of fluconazole in normal volunteers. Chemotherapy 1993; 39: 6–12.CrossRefPubMed
168.
Debruyne D, Ryckelynck J-P. Clinical pharmacokinetics of fluconazole. Clin Pharmacokinet 1993; 24: 10–27.CrossRefPubMed
169.
von Moltke LL, Greenblatt DJ, Granda BW, et al. Zolpidem metabolism in vitro: responsible cytochromes, chemical inhibitors, and in vivo correlations. Br J Clin Pharmacol 1999; 48: 89–97.CrossRef
170.
Negroni R, Arechavala AI. Itraconazole: pharmacokinetics and indications. Arch Med Res 1993; 24: 387–93.PubMed
171.
Humbert H, Cabiac MD, Denouël J, et al. Pharmacokinetics of terbinafine and of its five main metabolites in plasma and urine, following a single oral dose in healthy subjects. Biopharm Drug Dispos 1995; 16: 685–94.CrossRefPubMed
172.
Kovarik JM, Mueller EA, Zehender H, et al. Multiple-dose pharmacokinetics and distribution in tissue of terbinafine and its metabolites. Antimicrob Agents Chemother 1995; 39: 2738–41.CrossRefPubMed
173.
Thummel KE, O’shea D, Paine MF, et al. Oral first-pass elimination of midazolam involves both gastrointestinal and hepatic CYP3 A-mediated metabolism. Clin Pharmacol Ther 1996; 59: 491–502.CrossRefPubMed
174.
Gomez DY, Wacher VJ, Tomlanovich SJ, et al. The effects of ketoconazole on the intestinal metabolism and bioavailability of cyclosporine. Clin Pharmacol Ther 1995; 58: 15–9.CrossRefPubMed
175.
Floren LC, Bekersky I, Benet LZ, et al. Tacrolimus oral bioavailability doubles with co-administration of ketoconazole. Clin Pharmacol Ther 1997; 62: 41–9.CrossRefPubMed
176.
Isohanni MH, Neuvonen PJ, Palkama VJ, et al. Effect of erythromycin and itraconazole on the pharmacokinetics of intravenous lig-nocaine. Eur J Clin Pharmacol 1998; 54: 561–5.CrossRefPubMed
177.
Greenblatt DJ, Wright CE, von Moltke LL, et al. Ketoconazole inhibition of triazolam and alprazolam clearance: differential kinetic and dynamic consequences. Clin Pharmacol Ther 1998; 64: 237–47.CrossRefPubMed
178.
Van Tyle JH. Ketoconazole: mechanism of action, spectrum of activity, pharmacokinetics. drug interactions, adverse reactions and therapeutic use. Pharmacotherapy 1984; 4: 343–73.
179.
Bailey EM, Krakovsky DJ, Rybak MJ. The triazole antifungal agents: a review of itraconazole and fluconazole. Pharmacotherapy 1990; 10: 136–53.
180.
Backman JT, Kivistö KT, Olkkola KT, et al. The area under the plasma concentration-time curve for oral midazolam is 400-fold larger during treatment with itraconazole than with rifampicin. Eur J Clin Pharmacol 1998; 54: 53–8.CrossRefPubMed
181.
Yasui N, Kondo T, Otani K, et al. Effect of itraconazole on the single oral dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology 1998; 139: 269–73.CrossRefPubMed
182.
Kivistö KT, Lamberg TS, Neuvonen PJ. Interactions of buspirone with itraconazole and rifampicin: effects on the pharmacokinetics of the active l-(2-pyrimidinyl)-piperazine metabolite of buspirone. Pharmacol Toxicol 1999; 84: 94–7.CrossRefPubMed
183.
Isohanni MH, Neuvonen PJ, Olkkola KT. Effect of erythromycin and itraconazole on the pharmacokinetics of oral lignocaine. Pharmacol Toxicol 1999; 84: 143–6.CrossRefPubMed
184.
Faergemann J, Zehender H, Denouël J, et al. Levels of terbinafine in plasma, stratum corneum, dermis-epidermis (without stratum corneum), sebum, hair and nails during and after 250 mg terbinafine orally once per day for four weeks. Acta Derm Venereol 1993; 73: 305–9.PubMed
185.
Tett S, Moore S, Ray J. Pharmacokinetics and bioavailability of fluconazole in two groups of males with human immunodeficiency virus (HIV) infection compared with those in a group of males without HIV infection. Antimicrob Agents Chemother 1995; 39: 1835–41.CrossRefPubMed
186.
McLachlan AJ, Tett SE. Pharmacokinetics of fluconazole in people with HIV infection: a population analysis. Br J Clin Pharmacol 1996; 41: 291–8.CrossRefPubMed
187.
Kronbach T, Fischer V, Meyer UA. Cyclosporine metabolism in human liver: identification of a cytochrome P-450III gene family as the major cyclosporine-metabolizing enzyme explains interactions of cyclosporine with other drugs. Clin Pharmacol Ther 1988; 43: 630–5.CrossRefPubMed
188.
Kolars JC, Awni WM, Merion RM, et al. First-pass metabolism of cyclosporin by the gut. Lancet 1991; 338: 1488–90.CrossRefPubMed
189.
Jones TE. The use of other drugs to allow a lower dosage of cyclosporin to be used. Clin Pharmacokinet 1997; 32: 357–67.CrossRefPubMed
190.
Henricsson S, Lindholm A, Aravoglou M. Cyclosporin metabolism in human liver microsomes and its inhibition by other drugs. Pharmacol Toxicol 1990; 66: 49–52.CrossRefPubMed
191.
Shah IA, Whiting PH, Omar G, et al. The effects of retinoids and terbinafine on the human hepatic microsomal metabolism of cyclosporin. Br J Dermatol 1993; 129: 395–8.CrossRefPubMed
192.
Gomez D, Hébert M, Benet LZ. The effect of ketoconazole on the intestinal metabolism and bio availability of cyclosporine. Clin Pharmacol Ther 1994; 55: 209.
193.
Ferguson RM, Sutherland DE, Simmons RL, et al. Ketoconazole. cyclosporin metabolism, and renal transplantation. Lancet 1982; 2: 882–3.
194.
195.
Morgenstern GR, Powles R, Robinson B, et al. Cyclosporin interaction with ketoconazole and melphalan. Lancet 1982; 2: 1342.CrossRefPubMed
196.
Charles BG, Ravenscroft PJ, Rigby RJ. The ketoconazole-cyclosporin interaction in an elderly renal transplant patient. Aust NZ J Med 1989; 19: 292–3.CrossRef
197.
Albengres E, Tillement JP. Cyclosporin and ketoconazole. drug interaction or therapeutic association? Int J Clin Pharmacol Ther Toxicol 1992; 30: 555–70.PubMed
198.
Krüger HU, Schuler U, Zimmermann R, et al. Absence of significant interaction of fluconazole with cyclosporin. J Antimicrob Chemother 1989; 24: 781–6.CrossRefPubMed
199.
Canafax DM, Graves NM, Hilligoss DM, et al. Increased cyclosporine levels as a result of simultaneous fluconazole and cyclosporine therapy in renal transplant recipients: a double-blind, randomized pharmacokinetic and safety study. Transplant Proc 1991; 23: 1041–2.PubMed
200.
Canafax DM, Graves NM, Hilligoss DM, et al. Interaction between cyclosporine and fluconazole in renal allograft recipients. Transplantation 1991; 51: 1014–8.CrossRefPubMed
201.
Osowski CL, Dix SP, Lin LS, et al. Evaluation of the drug interaction between intravenous high-dose fluconazole and cyclosporine or tacrolimus in bone marrow transplant patients. Transplantation 1996; 61: 1268–72.CrossRefPubMed
202.
Kramer MR, Merin G, Rudis E, et al. Dose adjustment and cost of itraconazole prophylaxis in lung transplant recipients receiving cyclosporine and tacrolimus (FK506). Transplant Proc 1997; 29: 2657–9.CrossRefPubMed
203.
First MR, Schroeder TJ, Alexander JW, et al. Cyclosporin dose reduction by ketoconazole administration in renal transplant recipients. Transplantation 1991; 51: 365–70.CrossRefPubMed
204.
Butman SM, Wild JC, Nolan PE, et al. Prospective study of the safety and financial benefit of ketoconazole as adjunctive therapy to cyclosporine after heart transplantation. J Heart Lung Transplant 1991; 10: 351–8.PubMed
205.
First MR, Schroeder TJ, Michael A, et al. Safety and efficacy of longterm cyclosporine-ketoconazole administration and preliminary results of a randomized trial. Transplant Proc 1993; 25: 591–4.PubMed
206.
First MR, Schroeder TJ. Michael A, et al. Cyclosporine-ketoconazole interaction: long-term follow up and preliminary results of a randomized trial. Transplantation 1993; 55: 1000–4.
207.
Patton PR, Brunson ME, Pfaff WW, et al. A preliminary report of diltiazem and ketoconazole: their cyclosporine-sparing effect and impact on transplant outcome. Transplantation 1994; 57: 889–92.CrossRefPubMed
208.
Sorenson AL, Lovdahl M, Hewitt JM, et al. Effects of ketoconazole on cyclosporine metabolism in renal allograft recipients. Transplant Proc 1994; 26: 2822.PubMed
209.
Sobh M, El-Agroudy A, Moustafa F, et al. Co-administration of ketoconazole to cyclosporin-treated kidney transplant recipients: a prospective randomized study. Am J Nephrol 1995; 15: 493–9.CrossRefPubMed
210.
Keogh A, Spratt P, McCosker C, et al. Ketoconazole to reduce the need for cyclosporine after cardiac transplantation. N England J Med 1995; 333: 628–33.CrossRef
211.
Moore LW, Alloway RR, Acchiardo SR, et al. Clinical observations of metabolic changes occurring in renal transplant recipients receiving ketoconazole. Transplantation 1996; 61: 537–41.CrossRefPubMed
212.
Odocha O, Kelly B, Trimble S, et al. Cost-containment strategies in transplantation: the utility of cyclosporine-ketoconazole combination therapy. Transplant Proc 1996; 28: 907–9.PubMed
213.
Foradori A, Mezzano S, Videla C, et al. Modification of the phar-macokinetics of cyclosporine A and metabolites by the concomitant use of Neoral and diltiazem or ketoconazole in stable adult kidney transplants. Transplant Proc 1998; 30: 1685–7.CrossRefPubMed
214.
Jensen P, Lehne G, Fauchald P, et al. Effect of oral terbinafme treatment on cyclosporin pharmacokinetics in organ transplant recipients with dermatophyte nail infection. Acta Dermatol Venereol 1996; 76: 280–1.
215.
First MR, Schroeder TJ, Weiskittel P, et al. Concomitant administration of cyclosporin and ketoconazole in renal transplant recipients. Lancet 1989; 2: 1198–201.CrossRefPubMed
216.
Schroeder TJ, Melvin DB, Clardy CW, et al. Use of cyclosporine and ketoconazole without nephrotoxicity in two heart transplant recipients. J Heart Transplant 1987; 6: 84–9.PubMed
217.
Girardet RE, Melo JC, Fox MS, et al. Concomitant administration of cyclosporine and ketoconazole for three and a half years in one heart transplant recipient. Transplantation 1989; 48: 887–90.CrossRefPubMed
218.
McLachlan AJ, Tett SE. Effect of metabolic inhibitors on cyclosporine pharmacokinetics using a population approach. Ther Drug Monit 1998; 20: 390–5.CrossRefPubMed
219.
Ramadan AM, Nussenblatt RB, de Smet MD. Long-term follow-up of patients with chronic uveitis affecting the posterior pole treated with combination cyclosporine and ketoconazole. Ophthalmology 1997; 104: 706–11.PubMed
220.
Silverstein BE, Wong IG. Reduction of cyclosporine dosage with ketoconazole in a patient with birdshot retinochoroidopathy. Am J Ophthalmol 1998; 125: 106–8.CrossRefPubMed
221.
Karlix JL, Cheng MA, Brunson ME, et al. Decreased cyclosporine concentrations with the addition of an H2-receptor antagonist in a patient on ketoconazole. Transplantation 1993; 56: 1554–5.PubMed
222.
Blum RA, D’Andrea DT, Florentino BM, et al. Increased gastric pH and the bio availability of fluconazole and ketoconazole. Ann Intern Med 1991; 114: 75–757.
223.
Kwan JTC, Foxall PJD, Davidson DGC, et al. Interaction of cyclosporin and itraconazole. Lancet 1987; 2: 282.CrossRefPubMed
224.
Trenk D, Brett W, Jähnchen E, et al. Time course of cyclo-sporin/itraconazole interaction. Lancet 1987; 2: 1335–6.CrossRefPubMed
225.
Kramer MR, Marshall SE, Denning DW, et al. Cyclosporine and itraconazole interaction in heart and lung transplant recipients. Ann Intern Med 1990; 113: 327–9.PubMed
226.
Ehninger G, Jaschonek K, Schuler U, et al. Interaction of fluconazole with cyclosporin. Lancet 1989; 2: 104–5.CrossRefPubMed
227.
Lazar JD, Wilner KD. Drug interactions with fluconazole. Rev Infect Dis 1990; 12: S327–S33.CrossRefPubMed
228.
Collignon P, Hurley B, Mitchell D. Interaction of fluconazole with cyclosporin. Lancet 1989; 1: 1262.CrossRefPubMed
229.
Sugar AM, Saunders C, Idelson BA, et al. Interaction of fluconazole and cyclosporine. Ann Intern Med 1989; 110: 844.PubMed
230.
Torregrosa V, De la Torre M, Campistol JM, et al. Interaction of fluconazole with ciclosporin A. Nephron 1992; 60: 125–6.CrossRefPubMed
231.
Löpez-Gil JA. Fluconazole-cyclosporine interaction: a dose dependent effect? Ann Pharmacother 1993; 27: 427–30.PubMed
232.
Pichard L, Gillet G, Fabre I, et al. Identification of the rabbit and human cytochromes P-450IIIA as the major enzymes involved in the N-de-methylation of diltiazem. Drug Metab Dispos 1990; 18: 711–9.PubMed
233.
Horton CM, Freeman CD, Nolan PE, et al. Cyclosporine interactions with miconazole and other azole-antimycotics: a case report and review of the literature. J Heart Lung Transplant 1992; 11: 1127–32.PubMed
234.
Lo ACY, Lui S-L, Lo W-K, et al. The interaction of terbinafine and cyclosporine A in renal transplant patients. Br J Clin Pharmacol 1997; 43: 340–1.PubMed
235.
Karanam BV, Vincent SH, Chiu SHL. FK506 metabolism in human livermicrosomes: investigation of the involvement of cytochrome P450 isozymes other than CYP3A4. Drug Metab Dispos 1994; 22: 811–4.PubMed
236.
Sattler M, Guengerich FP, Yun C-H, et al. Cytochrome P-450 3A enzymes are responsible for biotransformation of FK506 and rapamycin in man and rat. Drug Metab Dispos 1992; 20: 753–61.PubMed
237.
Iwasaki K, Matsuda H, Nagase K, et al. Effects of twenty-three drugs on the metabolism of FK506 by human liver microsomes. Res Commun Chem Pathol Pharmacol 1993; 82: 209–16.PubMed
238.
Furlan V, Parquin F, Penaud JF, et al. Interaction between tacrolimus and itraconazole in a heart-lung transplant recipient. Transplant Proc 1998; 30: 187–8.CrossRefPubMed
239.
Billaud EM, Guillemain R, Tacco F, et al. Evidence for a pharma-cokinetic interaction between itraconazole and tacrolimus in organ transplant patients. Br J Clin Pharmacol 1998; 46: 271–2.PubMed
240.
Assan R, Fredj G, Larger E, et al. FK506/fluconazole interaction enhances FK506 nephrotoxicity. Diabete Metab 1994; 20: 49–52.PubMed
241.
Manez R, Martin M, Raman V, et al. Fluconazole therapy in transplant recipients receiving FK506. Transplantation 1994; 57: 1521–3.PubMed
242.
Mieles L, Venkataramanan R, Yokoyama I, et al. Interaction between FK506 and clotrimazole in a liver transplant recipient. Transplantation 1991; 52: 1086–7.CrossRefPubMed
243.
Floren LC, Christians U, Zimmerman JJ, et al. Sirolimus oral bioavailability increases ten-fold with concomitant ketoconazole. Clin Pharmacol Ther 1999; 65: 159.CrossRef
244.
Greenblatt DJ, von Moltke LL, Harmatz JS, et al. Interaction of triazolam and ketoconazole. Lancet 1995; 345: 191.CrossRefPubMed
245.
Vanakoski J, Mattila MJ, Vainio P, et al. 150 mg fluconazole does not substantially increase the effects of 10 mg midazolam or the plasma midazolam concentrations in healthy subjects. Int J Clin Pharmacol Ther 1995; 33: 518–23.PubMed
246.
Ahonen J, Olkkola KT, Neuvonen PJ. The effect of the antimycotic itraconazole on the pharmacokinetics and pharmacodynamics of diazepam. Fundam Clin Pharmacol 1996; 10: 314–8.CrossRefPubMed
247.
Ahonen J, Olkkola KT, Neuvonen PJ. Lack of effect of antimycotic itraconazole on the pharmacokinetics or pharmaco dynamics of temazepam. Ther Drug Monit 1996; 18: 124–7.CrossRefPubMed
248.
Brown MW, Maldonado AL, Meredith CG, et al. Effect of ketoconazole on hepatic oxidative drug metabolism. Clin Pharmacol Ther 1985; 37: 290–7.CrossRefPubMed
249.
Spina E, Avenoso A, Campo GM, et al. Effect of ketoconazole on the pharmacokinetics of imipramine and desipramine in healthy subjects. Br J Clin Pharmacol 1997; 43: 315–8.CrossRefPubMed
250.
Tsunoda SM, Velez RL, Greenblatt DJ. Ketoconazole (K) inhibition of intestinal and hepatic cytochrome P450 3 A4 (CYP3 A4) activity using midazolam (M) as an in vivo probe. Clin Pharmacol Ther 1999; 65: 172.CrossRef
251.
Lam YWF, Ereshefsky L, Alfaro C, et al. In vivo inhibition of midazolam disposition by ketoconazole and fluoxetine, and comparison to in vitro prediction. Clin Pharmacol Ther 1999; 65: 143.CrossRef
252.
Kronbach T, Mathys D, Umeno M, et al. Oxidation of midazolam and triazolam by human liver cytochrome P450IIIA4. Mol Pharmacol 1989; 36: 89–96.PubMed
253.
Schwarz HJ. Pharmacokinetics and metabolism of temazepam in man and several animal species. Br J Clin Pharmacol 1979; 8: 23S–9S.CrossRefPubMed
254.
Yasumori T, Nagata K, Yang S, et al. Cytochrome P450 mediated metabolism of diazepam in human and rat: involvement of human CYP2C in N-demethylation in the substrate concentration-dependent manner. Pharmacogenetics 1993; 3: 291–301.CrossRefPubMed
255.
Gugler R, Jensen JC. Omeprazole inhibits oxidative drug metabolism. Gastroenterology 1985; 89: 1235–41.PubMed
256.
Laurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996; 30: 52–76.CrossRefPubMed
257.
Kotegawa T, Laurijssens BE, Greenblatt DJ. Metabolic, pharmaco-kinetic and pharmaco dynamic interactions of triazolam and ketoconazole in rats. Clin Pharmacol Ther 1999; 65: 142.CrossRef
258.
Wandel C, Böcker R, Böhrer H, et al. Midazolam is metabolized by at least three different cytochrome P450 enzymes. Br J Anaesth 1994; 73: 658–61.CrossRefPubMed
259.
Gorski JC, Hall SD, Jones DR, et al. Regioselective biotransforma-tionof midazolam of members of the human cytochrome P450 3A (CYP3A) subfamily. Biochem Pharmacol 1994; 47: 1643–53.CrossRefPubMed
260.
Gascon M-P, Dayer P. In vitro forecasting of drugs which may interfere with the biotransformation of midazolam. Eur J Clin Pharmacol 1991; 41: 573–8.CrossRefPubMed
261.
Venkatakrishnan K, von Moltke LL, Duan SX, et al. Kinetic characterization and identification of the enzymes responsible for the hepatic biotransformation of adinazolam and N-desmethyladinazolam. J Pharm Pharmacol 1998; 50: 265–74.CrossRefPubMed
262.
Pichard L, Gillet G, Bonfils C, et al. Oxidative metabolism of zolpidem by human liver cytochrome P450s. Drug Metab Dispos 1995; 23: 1253–62.PubMed
263.
Senda C, Kishimoto W, Sakai K, et al. Identification of human cytochrome P450 isoforms involved in the metabolism of brotizolam. Xenobiotica 1997; 27: 913–22.CrossRefPubMed
264.
von Moltke LL, Greenblatt DJ, Grassi JM, et al. Gepirone and l-(2-pyrimidinyl)-piperazine in vitro: human cytochromes mediating transformation and cytochrome inhibitory effects. Psychopharma-cology 1998; 140: 293–9.CrossRef
265.
Olesen OV, Linnet K. Metabolism of the tricyclic antidepressant amitriptyline by cDNA-expressed human cytochrome P450 enzymes. Pharmacology 1997; 55: 235–43.CrossRefPubMed
266.
Venkatakrishnan K, Greenblatt DJ, von Moltke LL, et al. Five distinct human cytochromes mediate amitriptyline N-demethylation in vitro: dominance of CYP 2C19 and 3A4. J Clin Pharmacol 1998; 38: 112–21.PubMed
267.
Schmider J, Greenblatt DJ, Harmatz JS, et al. Enzyme kinetic modelling as a tool to analyse the behaviour of cytochrome P450 catalysed reactions: application to amitriptyline N-demethylation. Br J Clin Pharmacol 1996; 41: 593–604.CrossRefPubMed
268.
Newberry DL, Bass SN, Mbanefo CO. A fluconazole/amitriptyline drug interaction in three male adults. Clin Infect Dis 1997; 24: 270–1.CrossRefPubMed
269.
Koyama E, Chiba K, Tani M, et al. Reappraisal of human CYP isoforms involved in imipramine N-demethylation and 2-hydroxylation: a study using microsomes obtained from putative extensive and poor metabolizers of S-mephenytoin and eleven recombinant human CYPs. J Pharmacol Exp Ther 1997; 281: 1199–210.PubMed
270.
Brϕsen K, Hansen JG, Nielsen KK, et al. Inhibition by paroxetine of desipramine metabolism in extensive but not in poor metabolizers of sparteine. Eur J Clin Pharmacol 1993; 44: 349–55.CrossRef
271.
Gannon RH, Anderson ML. Fluconazole-nortriptyline drug interaction. Ann Pharmacother 1992; 26: 1456–7.PubMed
272.
Venkatakrishnan K, von Moltke LL, Greenblatt DJ. Nortriptyline E- 10-hydroxylation in vitro is mediated by human CYP2D6 (high affinity) and CYP3 A4 (low-affinity): implications for interactions with enzyme-inducing drugs. J Clin Pharmacol 1999; 39: 567–77.CrossRefPubMed
273.
Nielsen KK, Flinois JP, Beaune P, et al. The biotransformation of clomipramine in vitro, identification of the cytochrome P450s responsible for the separate metabolic pathways. J Pharmacol Exp Ther 1996; 277: 1659–64.PubMed
274.
Black PN, Possible interaction between fluoxetine and itraconazole. Ann Pharmacotherapy 1995; 29: 1048–9.
275.
von Moltke LL, Greenblatt DJ, Grassi JM, et al. Citalopram and desmethylcitalopram in vitro: human cytochromes mediating transformation, and cytochrome inhibitory effects. Biol Psychiatry 1999; 46: 839–49.CrossRef
276.
Kobayashi K, Chiba K, Yagi T, et al. Identification of cytochrome P450 isoforms involved in citalopram N-demethylation by human liver microsomes. J Pharmacol Exp Ther 1997; 280: 927–33.PubMed
277.
Rochat B, Amey M, Gillet M, et al. Identification of three cytochrome P450 isozymes involved in N-demethylation of citalopram enantiomers in human liver microsomes. Pharmaco genetics 1997; 7: 1–10.
278.
Sindrup SH, Brϕsen K, Gram LF, et al. The relationship between paroxetine and the sparteine oxidation polymorphism. Clin Pharmacol Ther 1992; 51: 278–87.CrossRefPubMed
279.
Otton SV, Ball SE, Cheung SW, et al. Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol 1996; 41: 149–56.CrossRefPubMed
280.
Fogelman SM, Schmider J, Venkatakrishnan K, et al. O-and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology 1999; 20: 480–90.CrossRefPubMed
281.
Rotzinger S, Fang J, Baker GB. Trazodone is metabolized to m-chlorophenylpiperazine by CYP3A4 from human sources. Drug Metab Dispos 1998; 26: 572–5.PubMed
282.
von Moltke LL, Greenblatt DJ, Granda BW, et al. Nefazodone, metachlorophenylpiperazine, and their metabolites in vitro: cytochromes mediating transformation, and P450-3A4 inhibitory actions. Psychopharmacology 1999; 145: 113–22.CrossRef
283.
Pan LP, Wijnant P, De Vriendt C, et al. Characterization of the cytochrome P450 isoenzymes involved in the in vitro N-dealkylation of haloperidol. Br J Clin Pharmacol 1997; 44: 557–64.CrossRefPubMed
284.
Usuki E, Pearce R, Parkinson A, et al. Studies on the conversion of haloperidol and its tetrahydropyridine dehydration product to potentially neurotoxic pyridinium metabolites by human liver microsomes. Chem Res Toxicol 1996; 9: 800–6.CrossRefPubMed
285.
Pirmohamed M, Williams D, Madden S, et al. Metabolism and bioactivation of clozapine by human liver in vitro. J Pharmacol Exp Ther 1995; 272: 984–90.PubMed
286.
Eiermann B, Engel G, Johansson I, et al. The involvement of CYP1A2 and CYP3A4 in the metabolism of clozapine. Br J Clin Pharmacol 1997; 44: 439–46.CrossRefPubMed
287.
Tugnait M, Hawes EM, McKay G, et al. Characterization of the human hepatic cytochromes P450 involved in the in vitro oxidation of clozapine. Chem Biol Interact 1999; 118: 171–89.CrossRefPubMed
288.
Linnet K, Olesen OV. Metabolism of clozapine by cDNA-expressed human cytochrome P450 enzymes. Drug Metab Dispos 1997; 25: 1379–82.PubMed
289.
Dahl-Puustinen M-L, Lidén A, Aim C, et al. Disposition of perphenazine is related to polymorphic debrisoquin hydroxylation in human beings. Clin Pharmacol Ther 1989; 46: 78–81.CrossRefPubMed
290.
Huang M-L, Van Peer A, Woestenborghs R, et al. Pharmacokinetics of the novel antipsychotic agent risperidone and the prolactin response in healthy subjects. Clin Pharmacol Ther 1993; 54: 257–68.CrossRefPubMed
291.
Fang J, Bourin M, Baker GB. Metabolism of risperidone to 9-hydroxyrisperidone by human cytochromes P450 2D6 and 3A4. Naunyn-Schmiedeberg’s Arch Pharmacol 1999; 359: 147–51.CrossRef
292.
Cadle RM, Zenon GJ, Rodriguez-Barradas MC, et al. Fluconazole-induced symptomatic phenytoin toxicity. Ann Pharmacother 1994; 28: 191–5.PubMed
293.
Mitchell AS, Holland JT. Fluconazole and phenytoin: a predictable interaction. BMJ 1989; 298: 1315.CrossRefPubMed
294.
Howitt KM, Oziemski MA. Phenytoin toxicity induced by fluconazole. Med J Aust 1989; 151: 603–4.PubMed
295.
Veronese ME, Mackenzie PI, Doecke CJ, et al. Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cyto-chrome P4502C9. Biochem Biophys Res Commun 1991; 175: 1112–8.CrossRefPubMed
296.
Bajpai M, Roskos LK, Shen DD, et al. Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereo selective metabolism of phenytoin to its major metabolite. Drug Metab Dispos 1996; 24: 1401–3.PubMed
297.
Rolan PE, Somogyi AA, Drew MJR, et al. Phenytoin intoxication during treatment with parenteral miconazole. BMJ 1983; 287: 1760.CrossRefPubMed
298.
Jensen JC, Gugler R. Interaction between metronidazole and drugs eliminated by oxidative metabolism. Clin Pharmacol Ther 1985; 37: 407–10.CrossRefPubMed
299.
Blyden GT, Scavone JM, Greenblatt DJ. Metronidazole impairs clearance of phenytoin but not of alprazolam or lorazepam. J Clin Pharmacol 1988; 28: 240–5.PubMed
300.
Mϕlholm Hansen J, Siersbaek-Nielsen K, Skovsted L, et al. Potentiation of warfarin by co-trimoxazole. BMJ 1975; 2: 684.
301.
Mϕlholm Hansen J, Kampmann JP, Siersbaek-Nielsen K, et al. The effect of different sulfonamides on phenytoin metabolism in man. Acta Med Scand 1979; 624: 106–10.
302.
Spina E, Arena D, Scordo MG, et al. Elevation of plasma carbamazepine concentrations by ketoconazole in patients with epilepsy. Ther Drug Monit 1997; 19: 535–8.CrossRefPubMed
303.
Kerr BM, Thummel KE, Wurden CJ, et al. Human liver carbamaz-epine metabolism: role of CYP3A4 and CYP2C8 in 10,11-epoxide formation. Biochem Pharmacol 1994; 47: 1969–79.CrossRefPubMed
304.
Pirmohamed M, Kitteringham NR, Guenthner TM, et al. An investigation of the formation of cytotoxic. protein-reactive and stable metabolites from carbamazepine in vitro. Biochem Pharmacol 1992; 43: 1675–82.
305.
Tucker RM, Denning DW, Hanson LH, et al. Interaction of azoles withrifampin, phenytoin. and carbamazepine: in vitro and clinical observations. Clinical Infectious Diseases 1992; 14: 165–74.
306.
Bonay M, Jonville-Bera AP, Diot P, et al. Possible interaction between phénobarbital, carbamazepine and itraconazole. Drug Saf 1993; 9: 309–11.CrossRefPubMed
307.
Nakasa H, Nakamura H, Ono S, et al. Prediction of drug-drug interactions of zonisamide metabolism in humans from in vitro data. Eur J Clin Pharmacol 1998; 54: 177–83.CrossRefPubMed
308.
Kivistö KT, Neuvonen PJ, Klotz U. Inhibition of terfenadine metabolism: pharmacokinetic and pharmacodynamic consequences. Clin Pharmacokinet 1994; 27: 1–5.CrossRefPubMed
309.
Monahan BP, Ferguson CL, Killeavy ES, et al. Torsades de pointes occurring in association with terfenadine use. JAMA 1990; 264: 2788–90.CrossRefPubMed
310.
Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clin Pharmacol Ther 1975; 18: 377–90.PubMed
311.
Greenblatt DJ. Presystemic extraction: mechanisms and consequences. J Clin Pharmacol 1993; 33: 650–6.PubMed
312.
Yun C-H, Okerholm RA, Guengerich FP. Oxidation of the antihistaminic drug terfenadine in human liver microsomes: role of cytochrome P-450 3A(4) in N-dealkylation and C-hydroxylation. Drug Metab Dispos 1993; 21: 403–9.PubMed
313.
Ling K-HJ, Leeson GA, Burmaster SD, et al. Metabolism of terfenadine associated with CYP3A(4) activity in human hepatic microsomes. Drug Metab Dispos 1995; 23: 631–6.PubMed
314.
Rodrigues AD, Mulford DJ, Lee RD, et al. In vitro metabolism of terfenadine by a purified recombinant fusion protein containing cytochrome P4503A4 and NADPH-P450 reductase. Drug Metab Dispos 1995; 23: 765–75.PubMed
315.
Lavrijsen KLM, Van Houdt JMG, Van Dick DMJ, et al. Induction potential of fluconazole toward drug metabolizing enzymes in rats. Antimicrob Agents Chemother 1990; 34: 402–8.CrossRefPubMed
316.
Kuang TY, Morgan A, Lazarev A, et al. Human CYP3A4 as a potential in vitro screening system for terfenadine drug interactions. Clin Pharmacol Ther 1994; 55: 139.
317.
Kuang TY, Cantilena LR. Terfenadine-ketoconazole metabolite interaction in human liver microsomes of male and female subjects. Clin Pharmacol Ther 1995; 57: 185.
318.
Kuang TY, Cantilena LR. Effect of ketoconazole on terfenadine enantiomeric metabolism in human liver slices, microsomes and S9 fractions. Clin Pharmacol Ther 1995; 57: 185.
319.
Li AP, Jurima-Romet M. Applications of primary human hepatocytes in the evaluation of pharmacokinetic drug-drug interactions: evaluation of model drugs terfenadine and rifampin. Cell Biol Toxicol 1997; 13: 365–74.CrossRefPubMed
320.
Honig PK, Wortham DC, Zamani K, et al. Terfenadine-ketoconazole interaction: pharmacokinetic and electro cardiographic consequences. JAMA 1993; 269: 1513–8.CrossRefPubMed
321.
Paserchia LA, Hewett J, Woosley RL. Effects of ketoconazole on QTc. Clin Pharmacol Ther 1994; 55: 146.
322.
Eller MG, Okerholm RA. Pharmacokinetic interaction between terfenadine and ketoconazole. Clin Pharmacol Ther 1991; 49: 130.
323.
Honig PK, Wortham DC, Hull R, et al. Itraconazole affects single-dose terfenadine pharmacokinetics and cardiac repolarization pharmacodynamics. J Clin Pharmacol 1993; 33: 1201–6.PubMed
324.
Pohjola-Sintonen S, Viita-Salo M, Toivonen L, et al. Torsades de pointes after terfenadine-itraconazole interaction. BMJ 1993; 306: 186.CrossRefPubMed
325.
Pohjola-Sintonen S, Viita-Salo M, Toivonen L, et al. Itraconazole prevents terfenadine metabolism and increases risk of torsades de pointes ventricular tachycardia. Eur J Clin Pharmacol 1993; 45: 191–3.CrossRefPubMed
326.
Crane JK, Shih H-T, Syncope and cardiac arrhythmia due to an interaction between itraconazole and terfenadine. Am J Med 1993; 95: 445–6.CrossRefPubMed
327.
Honig PK, Wortham DC, Zamani K, et al. The effect of fluconazole on the steady-state pharmacokinetics and electro cardiographie pharmacodynamics of terfenadine in humans. Clin Pharmacol Ther 1993; 53: 630–6.CrossRefPubMed
328.
Cantilena LR, Sorrels S, Wiley T, et al. Fluconazole alters terfenadine pharmacokinetics and electrocardiographic pharmacodynamics. Clin Pharmacol Ther 1995; 57: 185.
329.
Tsai W-C, Tsai L-M, Chen J-H. Combined use of astemizole and ketoconazole resulting in torsade de pointes. J Formosan Med Assoc 1997; 96: 144–6.PubMed
330.
Lefebvre RA, Van Peer A, Woestenborghs R. Influence of itraconazole on the pharmacokinetics and electrocardiographie effects of astemizole. Br J Clin Pharmacol 1997; 43: 319–22.CrossRefPubMed
331.
Yumibe N, Huie K, Chen K-J, et al. Identification of human liver cytochrome P450 enzymes that metabolize the nonsedating anti-histamine loratadine. Biochem Pharmacol 1996; 51: 165–72.CrossRefPubMed
332.
Van Peer A, Crabbé R, Woestenborghs R, et al. Ketoconazole inhibits loratadine metabolism in man. Allergy 1993; 48: 34.
333.
Brannan MD, Affrime MB, Radwanski E, et al. Effects of various cytochrome P450 inhibitors on the metabolism of loratadine. Clin Pharmacol Ther 1995; 57: 193.
334.
Imai T, Taketani M, Suzu T, et al. In vitro identification of the human cytochrome P-450 enzymes involved in the N-demethylation of azelastine. Drug Metab Dispos 1999; 27: 942–6.PubMed
335.
Morganroth J, Lyness WH, Perhach JL, et al. Lack of effect of azelastine and ketoconazole co-administration on electrocardio-graphic parameters in healthy volunteers. J Clin Pharmacol 1997; 37: 1065–72.PubMed
336.
Pesco-Koplowitz L, Hassell A, Lee P, et al. Lack of effect of eryth-romycin and ketoconazole on the pharmacokinetics and pharma-codynamics of steady-state intranasal levocabastine. J Clin Pharmacol 1999; 39: 76–85.CrossRefPubMed
337.
Glynn AM, Slaughter RL, Brass C, et al. Effects of ketoconazole on methylprednisolone pharmacokinetics and cortisol secretion. Clin Pharmacol Ther 1986; 39: 654–9.CrossRefPubMed
338.
Kandrotas RJ, Slaughter RL, Brass C, et al. Ketoconazole effects on methylprednisolone disposition and their joint suppression of endogenous cortisol. Clin Pharmacol Ther 1987; 42: 465–70.CrossRefPubMed
339.
Linthoudt H, Van Raemdonck D, Lerut T, et al. The association of itraconazole and methylprednisolone may give rise to important steroid-related side effects. J Heart Lung Transplant 1996; 15: 1165.PubMed
340.
Ludwig EA, Slaughter RL, Savliwala M, et al. Steroid-specific effects of ketoconazole on corticosteroid disposition: unaltered pre-dnisolone elimination. Drug Intell Clin Pharm 1989; 23: 858–61.
341.
Yamashita SK, Ludwig EA, Middleton E, et al. Lack of pharmacokinetic and pharmacodynamic interactions between ketoconazole and prednisolone. Clin Pharmacol Ther 1991; 49: 558–70.CrossRefPubMed
342.
Zürcher RM, Frey BM, Frey FJ. Impact of ketoconazole on the metabolism of prednisolone. Clin Pharmacol Ther 1989; 45: 366–72.CrossRefPubMed
343.
Jönsson G. Åström A, Andersson P. Budesonide is metabolized by cytochrome P450 3A (CYP3A) enzymes in human liver. Drug Metab Dispos 1995; 23: 137–42.
344.
Weisberg E. Interactions between oral contraceptives and antifun-gals/antibacterials: is contraceptive failure the result? Clin Phar-macokinet 1999; 36: 309–13.CrossRef
345.
Schmider J, Greenblatt DJ, von Moltke LL, et al. Biotransformation of mestranol to ethinyl estradiol in vitro: the role of cytochrome P-450 2C9 and metabolic inhibitors. J Clin Pharmacol 1997; 37: 193–200.PubMed
346.
Guengerich FP Oxidation of 17α-ethynylestradiol by human liver cytochrome P-450. Mol Pharmacol 1988; 33: 500–8.PubMed
347.
Pillans PL, Sparrow MJ. Pregnancy associated with a combined oral contraceptive and itraconazole. NZ Med J 1993; 106: 436.
348.
Meyboom RHB, van Puijenbroek EP, Vinks MHAM, et al. Disturbance of withdrawal bleeding during concomitant use of itraconazole and oral contraceptives. NZ Med J 1997; 110: 300.
349.
Kovács I, Somos P, Hámori M. Examination of the potential interaction between ketoconazole and oral contraceptives with special regard to products of low hormone content (Rigevidon, Anteovin). Ther Hung 1986; 34: 167–70.PubMed
350.
Sinofsky FE, Pasquale SA. The effect of fluconazole on circulating ethinyl estradiol levels in women taking oral contraceptives. Am J Obstet Gynecol 1998; 178: 300–4.CrossRefPubMed
351.
Joshi JV, Joshi UM, Sankholi GM, et al. A study of interaction of low-dose combination oral contraceptive with ampicillin and met-ronidazole. Contraception 1980; 22: 643–52.CrossRefPubMed
352.
van Dijke CPH, Weber JCP. Interaction between oral contraceptives and griseofulvin. BMJ 1984; 288: 1125–6.CrossRefPubMed
353.
McDaniel PA, Caldroney RD. Oral contraceptives and griseofulvin interaction. Drug Intell Clin Pharm 1986; 20: 384.PubMed
354.
Côté J. Interaction of griseofulvin and oral contraceptives. J Am Acad Dermatol 1990; 22: 124–5.CrossRefPubMed
355.
Swinney DC. Progesterone metabolism in hepatic microsomes: effect of the cytochrome P450 inhibitor, ketoconazole. and the NADPH 5α-reductase inhibitor. 4-MA, upon the metabolic profile in human, monkey, dog, and rat. Drug Metab Dispos 1990; 18: 859–65.
356.
Madden S, Back DJ, Orme MLE. Metabolism of the contraceptive steroid desogestrel by human liver in vitro. J Steroid Biochem 1990; 35: 281–8.CrossRefPubMed
357.
Rettie AE, Korzekwa KR, Kunze KL, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 1992; 5: 54–9.CrossRefPubMed
358.
359.
Gericke KR. Possible interaction between warfarin and fluconazole. Pharmacotherapy 1993; 13: 508–9.PubMed
360.
Crussell-Porter LL. Low-dose fluconazole therapy potentiates the hypoprothrombinemic response of warfarin sodium. Arch Intern Med 1993; 153: 102–4.CrossRefPubMed
361.
Seaton TL, Celum CL, Black DJ. Possible potentiation of warfarin by fluconazole. Drug Intell Clin Pharm 1990; 24: 1177–8.
362.
Kerr HD. Case report: potentiation of warfarin by fluconazole. Am J Med Sci 1993; 305: 164–5.CrossRefPubMed
363.
Baciewicz AM, Menke JJ, Bokar JA, et al. Fluconazole-warfarin interaction. Ann Pharmacother 1994; 28: 1111.PubMed
364.
365.
Brass C, Galgiani JN, Blaschke TF, et al. Disposition of ketoconazole, an oral antifungal, in humans. Antimicrob Agents Chemother 1982; 21: 151–8.CrossRefPubMed
366.
Yeh J, Soo S-C, Summerton C, et al. Potentiation of action of warfarin by itraconazole. BMJ 1990; 301: 669.CrossRefPubMed
367.
Watson PG, Lochan RG, Redding VJ. Drug interaction with coumarin derivative anticoagulants. BMJ 1982; 285: 1045–6.CrossRefPubMed
368.
369.
Colquhoun MC, Daly M, Stewart P, et al. Interaction between warfarin and miconazole oral gel. Lancet 1987; 1: 695–6.CrossRefPubMed
370.
Shenfield GM, Page M. Potentiation of warfarin action by miconazole oral gel. Aust NZ J Med 1991; 21: 928.CrossRef
371.
Pillans P, Woods DJ. Interaction between miconazole oral gel (Daktarin) and warfarin. NZ Med J 1996; 109: 346.
372.
Ariyaratnam S, Thakker NS, Sloan P, et al. Potentiation of warfarin anticoagulant activity by miconazole oral gel. BMJ 1997; 314: 349.CrossRefPubMed
373.
Hermans JJR, Thijssen HHW. Human liver microsomal metabolism of the enantiomers of warfarin and acenocoumarol: P450 isozyme diversity. Br J Pharmacol 1993; 110: 482–90.CrossRefPubMed
374.
Ortfn M, Olalla JI, Muruzábal MJ, et al. Miconazole oral gel enhances acenocoumarol anticoagulant activity: a report of three cases. Ann Pharmacother 1999; 33: 175–7.CrossRef
375.
O’Reilly RA. The stereo selective interaction of warfarin and metronidazole in man. N Engl J Med 1976; 295: 354–7.CrossRefPubMed
376.
Kazmier FJ. A significant interaction between metronidazole and warfarin. Mayo Clin Proc 1976; 51: 782–4.PubMed
377.
Gupta AK, Ross GS. Interaction between terbinafine and warfarin. Dermatology 1998; 196: 266–7.CrossRefPubMed
378.
Warwick JA, Corrall RJ. Serious interaction between warfarin and oral terbinafine. BMJ 1998; 316: 440.CrossRefPubMed
379.
Hassall C, Feetam CL, Leach RH, et al. Potentiation of warfarin by co-trimoxazole. Lancet 1975; 2: 1155–6.CrossRefPubMed
380.
Tilstone WJ, Nimmo-Smith RH, Gray JMB, et al. Interaction between warfarin and sulfamethoxazole. Postgrad Med J 1977; 53: 388–90.CrossRefPubMed
381.
Errick JK, Keys PW. Co-trimoxazole and warfarin: case report of an interaction. Am J Hosp Pharm 1978; 35: 1399–401.PubMed
382.
Greenlaw CW. Drug interaction between co-trimoxazole and warfarin. Am J Hosp Pharm 1979; 36: 1155–6.PubMed
383.
Kaufman JM, Fauver HE. Potentiation of warfarin by trimethoprim-sulfamethoxazole. Urology 1980; 16: 601–3.CrossRefPubMed
384.
Cook DE, Ponte CD. Suspected trimethoprim/sulfamethoxazole-induced hypoprothrombinemia. J Fam Pract 1994; 39: 589–91.PubMed
385.
O’Reilly RA, Motley CH. Racemic warfarin and trimethoprim-sulfamethoxazole interaction in humans. Ann Intern Med 1979; 295: 34–6.
386.
Engel G, Hofman U, Heidemann H, et al. Antipyrine as a probe for human oxidative drug metabolism: identification of the cytochrome P450 enzymes catalyzing 4-hydroxy methylantipyrine, and norantipyrine formation. Clin Pharmacol Ther 1996; 59: 613–23.CrossRefPubMed
387.
Sharer J, Wrighton S. Identification of human hepatic cytochromes P450 involved in the in vitro oxidation of antipyrine. Drug Metab Dispos 1996; 24: 487–94.PubMed
388.
Blyden GT, Abernethy DR, Greenblatt DJ. Ketoconazole does not impair antipyrine clearance in humans. Int J Clin Pharmacol Ther Toxicol 1986; 24: 225–6.PubMed
389.
D’Mello AR D’souza MJ, Bates TR. Pharmacokinetics of ketoconazole-antipyrine interaction. Lancet 1985; 2: 209–10.CrossRefPubMed
390.
Welch RM, DeAngelis RL, Wingfield M, et al. Elimination of antipyrine from saliva as a measure of metabolism in man. Clin Pharmacol Ther 1975; 18: 249–58.PubMed
391.
Vesell ES, Passananti GT, Glenwright PA, et al. Studies on the disposition of antipyrine. aminopyrine, and phenacetin using plasma, saliva, and urine. Clin Pharmacol Ther 1975; 18: 259–72.
392.
Purba HS, Back DJ. Effect of fluconazole (UK-49,858) on antipyrine metabolism. Br J Clin Pharmacol 1986; 21: 603P.
393.
Brockmeyer NH, Tillmann I, Mertins L, et al. Pharmacokinetic interaction of fluconazole and zidovudine in HIV-positive patients. Eur J Med Res 1997; 2: 377–83.PubMed
394.
Seyffer R, Eichelbaum M, Jensen JC, et al. Antipyrine metabolism is not affected by terbinafme, a new antifungal agent. Eur J Clin Pharmacol 1989; 37: 231–3.CrossRefPubMed
395.
396.
Heusner JJ, Dukes GE, Rollins DE, et al. Effect of chronically administered ketoconazole on the elimination of theophylline in man. Drug Intell Clin Pharm 1987; 21: 514–7.PubMed
397.
Tjia JF, Colbert J, Back DJ. Theophylline metabolism in human liver microsomes: inhibition studies. J Pharmacol Exp Ther 1996; 276: 912–7.PubMed
398.
Murphy E, Hannon D, Callaghan B. Ketoconazole-theophylline interaction. Ir Med J 1987; 80: 123–4.PubMed
399.
Ha HR, Chen J, Freiburghaus AU, et al. Metabolism of theophylline by cDNA-expressed human cytochromes P-450. Br J Clin Pharmacol 1995; 39: 321–6.CrossRefPubMed
400.
Zhang Z-Y, Kaminsky LS. Characterization of human cytochromes P450 involved in theophylline 8-hydroxylation. Biochem Pharmacol 1995; 50: 205–11.CrossRefPubMed
401.
Ha HR, Chen J, Krähenbühl S, et al. Biotransformation of caffeine by cDNA-expressed human cytochromes P-450. Eur J Clin Pharmacol 1996; 49: 309–15.CrossRefPubMed
402.
Miners JO, Birkett DJ. The use of caffeine as a metabolic probe for human drug metabolizing enzymes. Gen Pharmacol 1996; 27: 245–9.CrossRefPubMed
403.
Konishi H, Morita K, Yamaji A. Effect of fluconazole on theophylline disposition in humans. Eur J Clin Pharmacol 1994; 46: 309–12.CrossRefPubMed
404.
Nix DE, Zelenitsky SA, Symonds WT, et al. The effect of fluconazole on the pharmacokinetics of caffeine in young and elderly. Clin Pharmacol Ther 1992; 51: 183.
405.
Trépanier EF, Nafziger AN, Amsden GY. Effect of terbinafine on theophylline pharmacokinetics in healthy volunteers. Antimicrob Agents Chemother 1998; 42: 695–7.PubMed
406.
Trépanier EF, Nafziger AN, Kearns GL, et al. Absence of effect of terbinafine on the activity of CYP1A2, NAT-2, and xanthine ox-idase. J Clin Pharmacol 1998; 38: 424–8.PubMed
407.
Rasmussen BB, Jeppesen U, Gaist D, et al. Griseofulvin and fluvoxam-ine interactions with the metabolism of theophylline. Ther Drug Monit 1997; 19: 56–62.CrossRefPubMed
408.
Reitberg DB, Klarnet JP, Carlson JK, et al. Effect of metronidazole on theophylline pharmacokinetics. Clin Pharm 1983; 2: 441–4.PubMed
409.
Adebayo GI, Mabadeje FB. Lack of inhibitory effect of metronidazole on theophylline disposition in healthy subjects. Br J Clin Pharmacol 1987; 24: 110–3.CrossRefPubMed
410.
Heinig R, Adelmann HG, Ahr G. The effect of ketoconazole on the pharmacokinetics, pharmacodynamics and safety of nisoldipine. Eur J Clin Pharmacol 1999; 55: 57–60.CrossRefPubMed
411.
Ueno K, Yamaguchi R, Tanaka K, et al. Lack of a kinetic interaction between fluconazole and mexiletine. Eur J Clin Pharmacol 1996; 50: 129–31.CrossRefPubMed
412.
Partanen J, Jalava K-M, Neuvonen PJ. Itraconazole increases serum digoxin concentration. Pharmacol Toxicol 1996; 79: 274–6.CrossRefPubMed
413.
McCrea JB, Lo MW, Furtek CI, et al. Ketoconazole does not effect the systemic conversion of losartan to E-3174. Clin Pharmacol Ther 1996; 59: 169.CrossRef
414.
Kazierad DJ, Martin DE, Blum RA, et al. Effect of fluconazole on the pharmacokinetics of eprosartan and losartan in healthy male volunteers. Clin Pharmacol Ther 1997; 62: 417–25.CrossRefPubMed
415.
Kovacs SJ, Wilton JH, Blum RA. Steady state (SS) pharmacokinetics (PK) of irbesartan alone and in combination with fluconazole (F). Clin Pharmacol Ther 1999; 65: 132.
416.
Guengerich FP, Brian WR, Iwasaki M, et al. Oxidation of dihydropyrid-ine calcium channel blockers and analogues by human liver cyto-chrome P-450 IIIA4. J Med Chem 1991; 34: 1838–44.CrossRefPubMed
417.
Tailor SAN, Gupta AK, Walker SE, et al. Peripheral edema due to nifedipine-itraconazole interaction: a case report. Arch Dermatol 1996; 132: 350–2.CrossRefPubMed
418.
Neuvonen PJ, Suhonen R. Itraconazole interacts with felodipine. J Am Acad Dermatol 1995; 33: 134–5.CrossRefPubMed
419.
Kremens B, Brendel E, Bald M, et al. Loss of blood pressure control on withdrawal of fluconazole during nifedipine therapy. Br J Clin Pharmacol 1999; 47: 707–8.PubMed
420.
Kroemer HK, Echizen H, Heidemann H, et al. Predictability of the in vivo metabolism of verapamil from in vitro data: contribution of individual metabolic pathways and stereo selective aspects. J Pharmacol Exp Ther 1992; 260: 1052–7.PubMed
421.
Kroemer HK, Gautier JC, Beaune P, et al. Identification of P450 enzymes involved in metabolism of verapamil in humans. Naunyn-Schmiedeberg’s Arch Pharmacol 1993; 348: 332–7.
422.
Busse D, Cosme J, Beaune P, et al. Cytochromes of the P4502C subfamily are the major enzymes involved in the O-demethylation of verapamil in humans. Naunyn-Schmiedeberg’s Arch Pharmacol 1995; 353: 116–21.
423.
Sandström R, Knutson TW, Knutson L, et al. The effect of ketoconazole on the jejunal permeability and CYP3A metabolism of (R/S)-verapamil in humans. Br J Clin Pharmacol 1999; 48: 180–9.CrossRefPubMed
424.
Fabre G, Julian B, Saint-Aubert B, et al. Evidence for CYP3A-mediated N-deethylation of amiodarone in human liver microsomal fractions. Drug Metab Dispos 1993; 21: 978–85.PubMed
425.
Guengerich FP, Müller-Enoch D, Blair IA. Oxidation of quinidine by human liver cytochrome P450. Mol Pharmacol 1986; 30: 287–95.PubMed
426.
Bargetzi MJ, Aoyama T, Gonzalez FJ, et al. Lidocaine metabolism by human liver microsomes by cytochrome P450IIIA4. Clin Pharmacol Ther 1989; 46: 521–7.CrossRefPubMed
427.
Kroemer HK, Mikus G, Kronbach T, et al. In vitro characterization of the human cytochrome P-450 involved in polymorphic oxidation of propafenone. Clin Pharmacol Ther 1989; 45: 28–33.CrossRefPubMed
428.
Lee JT, Kroemer HK, Silberstein DJ, et al. The role of genetically determined polymorphic drug metabolism in beta-blockade produced by propafenone. N Engl J Med 1990; 322: 1764–8.CrossRefPubMed
429.
Funck-Brentano C, Turgeon J, Woosley RL, et al. Effect of low dose quinidine on encainide pharmacokinetics and pharmacodynamics. Influence of genetic polymorphism. J Pharmacol Exp Ther 1989; 249: 134–42.
430.
McNulty RM, Lazor JA, Sketch M. Transient increase in plasma quinidine concentrations during ketoconazole-quinidine therapy. Clin Pharm 1989; 8: 222–5.PubMed
431.
Mörike K, Magadum S, Mettang T, et al. Propafenone in a usual dose produces severe side effects: the impact of genetically determined metabolic status on drug therapy. J Intern Med 1995; 238: 469–72.CrossRefPubMed
432.
Vandamme N, Broly F, Libersa C, et al. Stereo selective hydroxylation of mexiletine in human liver microsomes: implication of P450IID6 - a preliminary report. J Cardiovasc Pharmacol 1993; 21: 77–83.CrossRefPubMed
433.
Abolfathi Z, Padkel H, Beaune P, et al. CYP1A2 is the majorenzyme involved in the N-oxidation of mexiletine (MEX) in man. Clin Pharmacol Ther 1995; 57: 215.
434.
Rex J. Itraconazole-digoxin interaction. Ann Intern Med 1992; 116: 525.PubMed
435.
Kaufmann CA, Bagnasco FA. Digoxin toxicity associated with itraconazole therapy. Clin Infect Dis 1992; 15: 886–7.CrossRef
436.
Sachs MK, Blanchard LM, Green PJ. Interaction of itraconazole and digoxin. Clin Infect Dis 1993; 16: 400–3.CrossRefPubMed
437.
Alderman CP, Allcroft PD. Digoxin-itraconazole interaction: possible mechanisms. Ann Pharmacother 1997; 31: 438–40.PubMed
438.
McClean KL, Sheehan GJ. Interaction between itraconazole and digoxin. Clin Infect Dis 1994; 18: 259–60.CrossRefPubMed
439.
Cone LA, Himelman RB, Hirschberg JN, et al. Itraconazole-related amaurosis and vomiting due to digoxin toxicity. West J Med 1996; 165: 322.PubMed
440.
Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole. N Engl J Med 1995; 333: 664–5.CrossRefPubMed
441.
Horn M. Coadministration of itraconazole with hypolipidemic agents may induce rhabdomyolysis in healthy individuals. Arch Dermatol 1996; 132: 1254.CrossRefPubMed
442.
Wang RW, Kari PH, Lu AYR, et al. Biotransformation of lovastatin IV. Identification of cytochrome P450 3A proteins as the major enzymes responsible for the oxidative metabolism of lovastatin in rat and human liver microsomes. Arch Biochem Biophys 1991; 290: 355–61.CrossRefPubMed
443.
Jacobsen W, Kirchner G, Hallensleben K, et al. Comparison of cytochrome P-450-dependent metabolism and drug interactions of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos 1999; 27: 173–9.PubMed
444.
Prueksaritanont T, Gorham LM, Ma B, et al. In vitro metabolism of simvastatin in humans [SBT] identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 1997; 25: 1191–9.PubMed
445.
Lennernäs H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet 1997; 32: 403–25.CrossRefPubMed
446.
Prueksaritanont T, Ma B, Tang C, et al. Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: an in vitro investigation with human liver preparations. Br J Clin Pharmacol 1999; 47: 291–8.CrossRefPubMed
447.
Transon C, Leeman T, Dayer P. In vitro comparative inhibition profiles of major human drug metabolising cytochrome P450 isozymes (CYP2C9, CYP2D6 and CYP3A4) by HMG-CoA reductase inhibitors. Eur J Clin Pharmacol 1996; 50: 209–15.CrossRefPubMed
448.
Transon C, Leemann T, Vogt N, et al. In vivo inhibition profile of cytochrome P450tb (CYP2C9) by (±)-fluvastatin. Clin Pharmacol Ther 1995; 58: 412–7.CrossRefPubMed
449.
Stearns RA, Chakravarty PK, Chen R, et al. Biotransformation of losartan to its active carboxylic acid metabolite in human liver microsomes: role of cytochrome P4502C and 3A subfamily members. Drug Metab Dispos 1995; 23: 207–15.PubMed
450.
Belpaire FM, Wijnant P, Temmerman A, et al. The oxidative metabolism of metoprolol in human liver microsomes: inhibition by the selective serotonin reuptake inhibitors. Eur J Clin Pharmacol 1998; 54: 261–4.CrossRefPubMed
451.
Otton SV, Crewe HK, Lennard MS, et al. Use of quinidine inhibition to define the role of the sparteine/debrisoquine cytochrome P450 in metoprolol oxidation by human liver microsomes. J Pharmacol Exp Ther 1988; 247: 242–7.PubMed
452.
Masubuchi Y, Hosokawa S, Horie T, et al. Cytochrome P450 isozymes involved in propranolol metabolism in human liver microsomes: the role of CYP2D6 as ring-hydroxylase and CYP1A2 as N-deisopropylase. Drug Metab Dispos 1994; 22: 909–15.PubMed
453.
Yoshimoto K, Echizen H, Chiba K, et al. Identification of human CYP isoforms involved in the metabolism of propranolol en-antiomers — N-deisopropylation is mediated mainly by CYP1A2. Br J Clin Pharmacol 1995; 39: 421–31.CrossRefPubMed
454.
Rowland K, Ellis SW, Lennard MS, et al. Variable contribution of CYP2D6 to the N-dealkylation of S-(−)-propranolol by human liver microsomes. Br J Clin Pharmacol 1996; 42: 390–3.CrossRefPubMed
455.
Kudo S, Uchida M, Odomoi M, Metabolism of carteolol by cDNA-expressed human cytochrome P450. Eur J Clin Pharmacol 1997; 52: 479–85.CrossRefPubMed
456.
McGourty JC, Silas JH, Fleming JJ, et al. Pharmacokinetics and beta-blocking effects of timolol in poor and extensive metabo-lizers of debrisoquin. Clin Pharmacol Ther 1985; 38: 409–13.CrossRefPubMed
457.
Zhou H-H, Wood AJJ. Stereo selective disposition of carvedilol is determined by CYP2D6. Clin Pharmacol Ther 1995; 57: 518–24.CrossRefPubMed
458.
Oldham HG, Clarke SE. In vitro identification of the human cytochrome P450 enzymes involved in the metabolism of R-(+)- and S-(−)-carvedilol. Drug Metab Dispos 1997; 25: 970–7.PubMed
459.
Rowe BR, Thorpe J, Barnett A. Safety of fluconazole in women taking oral hypoglycaemic agents. Lancet 1992; 339: 255–6.CrossRefPubMed
460.
Miners JO, Birkett DJ. Use of tolbutamide as a substrate probe for human hepatic cytochrome P450 2C9. Methods Enzymol 1996; 272: 139–45.CrossRefPubMed
461.
Doble N, Shaw R, Rowland-Hill C, et al. Pharmacokinetic study of the interaction between rifampicin and ketoconazole. J Anti-microb Chemother 1988; 21: 633–5.
462.
Engelhard D, Stutman HR, Marks MI. Interaction of ketoconazole with rifampin and isoniazid. N Engl J Med 1984; 311: 1681–3.CrossRefPubMed
463.
Abadie-Kemmerly S, Pankey GA, Dalvisio JR. Failure of ketoconazole treatment of Blastomyces dermatidis due to interaction of isoniazid and rifampin. Ann Intern Med 1988; 109: 844–5.PubMed
464.
Apseloff G, Hilligoss DM, Gardner MJ, et al. Induction of fluconazole metabolism by rifampin: in vivo study in humans. J Clin Pharmacol 1991; 31: 358–61.PubMed
465.
Coker RJ, Tomlinson DR, Parkin J, et al. Interaction between fluconazole and rifampicin. BMJ 1990; 301: 818.CrossRefPubMed
466.
Nicolau DP, Crowe HM, Nightingale CH, et al. Rifampin-fluconazole interaction in critically ill patients. Ann Pharmacother 1995; 29: 994–6.PubMed
467.
Jaruratanasirikul S, Kleepkaew A. Lack of effect of fluconazole on the pharmacokinetics of rifampicin in AIDS patients. J Antimicrob Chemother 1996; 38: 877–80.CrossRefPubMed
468.
Drayton J, Dickinson G, Rinaldi MG. Coadministration of rifampin and itraconazole leads to undetectable levels of serum itraconazole. Clin Infect Dis 1994; 18: 266.CrossRefPubMed
469.
Trapnell CB. Increased plasma rifabutin levels with concomitant fluconazole therapy in HIV-infected patients. Ann Intern Med 1996; 124: 573–6.PubMed
470.
Narang PK, Trapnell CB, Schoenfelder JR, et al. Fluconazole and enhanced effect of rifabutin prophylaxis. N Engl J Med 1994; 330: 1316–7.CrossRefPubMed
471.
Fuller JD, Stanfield LED, Craven DE. Rifabutin prophylaxis and uveitis. N Engl J Med 1994; 330: 1315–6.CrossRefPubMed
472.
Trapnell CB, Jamis-Dow C, Klecker RW, et al. Metabolism of rifabutin and its 25-desacetyl metabolite. LM565. by human liver microsomes and recombinant human cytochrome P-450 3 A4: relevance to clinical interaction with fluconazole. Antimicrob Agents Chemother 1997; 41: 924–6.
473.
Skinner MH, Hsieh M, Torseth J, et al. Pharmacokinetics of rifabutin. Antimicrob Agents Chemother 1989; 33: 1237–41.CrossRefPubMed
474.
Lefort A, Launay O, Carbon C. Uveitis associated with rifabutin prophylaxis and itraconazole therapy. Ann Intern Med 1996; 125: 939–40.PubMed
475.
Gill HJ, Tingle MD, Park BK. N-Hydroxylation of dapsone by multiple enzymes of cytochrome P450: implications for inhibition of haemotoxicity. Br J Clin Pharmacol 1995; 40: 531–8.CrossRefPubMed
476.
Mitra AK, Thummel KE, Kalhorn TF, et al. Metabolism of dapsone to its hydroxylamine by CYP2E1 in vitro and in vivo. Clin Pharmacol Ther 1995; 58: 556–66.CrossRefPubMed
477.
Kinirons MT, Krivoruk Y Wilkinson GR, et al. Effects of ketoconazole on the erythromycin breath test and the dapsone recovery ratio. Br J Clin Pharmacol 1999; 47: 223–5.PubMed
478.
Cribb AE, Spielberg SP, Griffin GP. N4-Hydroxylation of sulfamethoxazole by cytochrome P450 of the cytochrome P4502C subfamily and reduction of sulfamethoxazole hydroxylamine in human and rat hepatic microsomes. Drug Metab Dispos 1995; 23: 406–14.PubMed
479.
Zhao X-J, Yokoyama H, Chiba K, et al. Identification of human cytochrome P450 isoforms involved in the 3-hydroxylation of quinine by human liver microsomes and nine recombinant human cytochromes P450. J Pharmacol Exp Ther 1996; 279: 1327–34.PubMed
480.
Zhao X-J, Kawashiro T, Ishizaki T. Mutual inhibition between quinine and etoposide by human liver microsomes: evidence for cytochrome P4503A4 involvement in their major metabolic pathways. Drug Metab Dispos 1997; 26: 188–91.
481.
Kivistö KT, Kroemer HK, Eichelbaum M. The role of human cytochrome P450 enzymes in the metabolism of anticancer agents: implications for drug interactions. Br J Clin Pharmacol 1995; 40: 523–30.CrossRefPubMed
482.
Gillum JG, Israel DS, Polk RE. Pharmacokinetic drug interactions with antimicrobial agents. Clin Pharmacokinet 1993; 25: 450–82.CrossRefPubMed
483.
van Meerten E, Verweij J, Schellens JHM. Antineoplastic agents: drug interactions of clinical significance. Drug Saf 1995; 12: 168–82.CrossRefPubMed
484.
Rigas JR, Francis PA, Muindi JRF, et al. Constitutive variability in the pharmacokinetics of the natural retinoid, all-trans-retinoic acid, and its modulation by ketoconazole. J Natl Cancer Inst 1993; 85: 1921–6.CrossRefPubMed
485.
Lee JS, Newman RA, Lippman SM, et al. Phase I evaluation of all-trans-retinoic acid with and without ketoconazole in adults with solid tumors. J Clin Oncol 1995; 13: 1501–8.PubMed
486.
Schwarz EL, Hallam S, Gallagher RE, et al. Inhibition of ail-trans-retinoic acid metabolism by fluconazole in vitro and in patients with acute promyelocytic leukemia. Biochem Pharmacol 1995; 50: 923–8.CrossRef
487.
Muindi JF, Young CW. Lipid hydroperoxides greatly increase the rate of oxidative catabolism of all-trans-retinoic acid by human cell culture microsomes genetically enriched in specific cytochrome P-450 isoforms. Cancer Res 1993; 53: 1226–9.PubMed
488.
Walker D, Flinois J-P, Monkman SC, et al. Identification of the major human hepatic cytochrome P450 involved in activation and N-dechloroethylation of ifosfamide. Biochem Pharmacol 1994; 47: 1157–63.CrossRefPubMed
489.
Granvil CP Madan A, Sharkawi M, et al. Role of CYP2B6 and CYP3A4 in the in vitro N-dechloroethylation of (R)- and (S)-ifosfamide in human liver microsomes. Drug Metab Dispos 1999; 27: 533–41.PubMed
490.
Ninane J. A multicentre study of fluconazole versus oral polyenes in the prevention of fungal infection in children with hematolog-ical or oncological malignancies. Eur J Clin Microbiol Infect Dis 1994; 13: 330–7.CrossRefPubMed
491.
Yule SM, Walker D, Pearson ADJ, et al. Potential inhibition of al-kylating agent metabolism by fluconazole. Eur J Clin Microbiol Infect Dis 1994; 13: 1086–7.CrossRefPubMed
492.
Rotstein C, Bow EJ, Laverdiere M, et al. Randomized placebo-controlled trial of fluconazole prophylaxis for neutropenic cancer patients: benefit based on purpose and intensity of cytotoxic therapy. Clin Infect Dis 1999; 28: 331–40.CrossRefPubMed
493.
Yule SM, Walker D, Cole M, et al. The effect of fluconazole on cyclophosphamide metabolism in children. Drug Metab Dispos 1999; 27: 417–21.PubMed
494.
Buggia I, Zecca M, Alessandrino EP, et al. Itraconazole can increase systemic exposure to busulfan in patients given bone marrow transplantation. Anticancer Res 1996; 16: 2083–8.PubMed
495.
Murphy JA, Ross LM, Gibson BES. Vincristine toxicity in five children with acute lymphoblastic leukemia. Lancet 1995; 346: 443.CrossRefPubMed
496.
Gillies J, Hung KA, Fitzsimons E, et al. Severe vincristine toxicity in combination with itraconazole. Clin Lab Haematol 1998; 20: 123–4.CrossRefPubMed
497.
Rahman A, Korzekwa KR, Grogan J, et al. Selective biotransformation of taxol to 6α-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 1994; 54: 5543–6.PubMed
498.
Cresteil T, Monsarrat B, Alvinerie P, et al. Taxol metabolism by human liver microsomes: identification of cytochrome P450 iso-zymes involved in its biotransformation. Cancer Res 1994; 54: 386–92.PubMed
499.
Desai PB, Duan JZ, Zhu Y-W, et al. Human liver microsomal metabolism of paclitaxel and drug interactions. Eur J Drug Metab Pharmacokinet 1998; 23: 417–24.CrossRefPubMed
500.
Kawashiro T, Yamashita K, Zhao X-J, et al. A study on the metabolism of etoposide and possible interactions with antitumor or supporting agents by human liver microsomes. J Pharmacol Exp Ther 1998; 286: 1294–300.PubMed
501.
Haaz M-C, Rivory L, Riché C, et al. Metabolism of irinotecan (CPT-11) by human hepatic microsomes: participation of cytochrome P-450 3A and drug interactions. Cancer Res 1998; 58: 468–72.PubMed
502.
Rajaonarison JF, Lacarelle B, Catalin J, et al. 3-Azido-3′-deoxythymidine drug interactions: screening for inhibitors in human liver microsomes. Drug Metab Dispos 1992; 20: 578–84.PubMed
503.
Sampol E, Lacarelle B, Rajaonarison JF, et al. Comparative effects of antifungal agents on zidovudine glucuronidation by human liver microsomes. Br J Clin Pharmacol 1995; 40: 83–6.CrossRefPubMed
504.
Asgari M, Back DJ. Effect of azoles on the glucuronidation of zidovudine by human liver UDP-glucuronosyltransferase. J Infect Dis 1995; 172: 1634–5.CrossRefPubMed
505.
Trapnell CB, Klecker RW, Jamis-Dow C, et al. Glucuronidation of 3′-azido-3′-deoxythymidine (zidovudine) by human liver microsomes: relevance to clinical pharmacokinetic interactions with atovaquone, fluconazole. methadone, and valproic acid. Antimicrob Agents Chemother 1998; 42: 1592–6.
506.
Bozzette SA, Larsen RA, Chiu J, et al. A placebo-controlled trial of maintenance therapy with fluconazole after treatment of crypto-coccal meningitis in the acquired immunodeficiency syndrome. N Engl J Med 1991; 324: 580–4.CrossRefPubMed
507.
Canas E, Pachon J, Garcia-Pesquera F, et al. Absence of effect of trimethoprim-sulfamethoxazole on pharmacokinetics of zidovudine in patients infected with human immunodeficiency virus. Antimicrob Agents Chemother 1996; 40: 230–3.PubMed
508.
Bruzzese VL, Gillum JG, Israel DS, et al. Effect of fluconazole on pharmacokinetics of 2′, 3′-dideoxyinosine in persons seropositive for human immunodeficiency virus. Antimicrob Agents Chemother 1995; 39: 1050–3.CrossRefPubMed
509.
Kumar GN, Rodriguea AD, Buko AM, et al. Cytochrome P450-mediated metabolism of the HIV-1 protease inhibitor ritonavir (ABT-538) in human liver microsomes. J Pharmacol Exp Ther 1996; 277: 423–31.PubMed
510.
Koudriakova T, Iatsimirskaia E, Utkin I, et al. Metabolism of the human immunodeficiency virus protease inhibitors indinavir and ritonavir by human intestinal microsomes and expressed cytochrome P4503A4/3A5: mechanism-based inactivation of cytochrome P4503A by ritonavir. Drug Metab Dispos 1998; 26: 552–61.PubMed
511.
Chiba M, Hensleigh M, Nishime JA, et al. Role of cytochrome P450 3A4 in human metabolism of MK-639, a potent human immunodeficiency virus protease inhibitor. Drug Metab Dispos 1996; 24: 307–14.PubMed
512.
Chiba M, Hensleigh M, Lin JH. Hepatic and intestinal metabolism of indinavir. an HIV protease inhibitor, in rat and human microsomes. Biochem Pharmacol 1997; 53: 1187–95.
513.
Kerr BM, Yuen GJ, Sandoval T, et al. The pharmacokinetics (PK) of nelfinavir (N) administered alone and with ketoconazole (K) in healthy volunteers [abstract]. Clin Pharmacol Ther 1997; 61: 147.
514.
Decker CJ, Laitinen LM, Bridson GW, et al. Metabolism of amprenavir in liver microsomes: role of CYP3A4 inhibition for drug interactions. J Pharm Sci 1998; 87: 803–7.CrossRefPubMed
515.
Alsenz J, Steffen H, Alex R. Active apical secretory efflux of the HIV protease inhibitors saquinavir and ritonavir in caco-2 cell monolayers. Pharm Res 1998; 15: 423–8.CrossRefPubMed
516.
Lee CG, Gottesman MM, Cardarelli CO, et al. HIV-1 protease inhibitors are substrates for the MDR1 multidrug transporter. Biochemistry 1998; 37: 3594–601.CrossRefPubMed
517.
Kim RB, Fromm ME Wandel C, et al. The drug transporter P-gly-coprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 1998; 101: 289–94.CrossRefPubMed
518.
Kim AE, Dintaman JM, Waddell DS, et al. Saquinavir, an HIV protease inhibitor, is transported by P-glycoprotein. J Pharmacol Exp Ther 1998; 286: 1439–45.PubMed
519.
Kakuda TN, Struble KA, Piscitelli SC. Protease inhibitors for the treatment of human immunodeficiency virus infection. Am J Health-System Pharm 1998; 55: 233–54.
520.
Cato A, Cao G, Hsu A, et al. Evaluation of the effect of fluconazole on the pharmacokinetics of ritonavir. Drug Metab Dispos 1997; 25: 1104–6.PubMed
521.
Kaul DR, Cinti SK, Carver PL, et al. HIV protease inhibitors: advances in therapy and adverse reactions, including metabolic complications. Pharmacotherapy 1999; 19: 281–98.CrossRefPubMed
522.
Jordan WC. The effectiveness of combined saquinavir and ketoconazole treatment in reducing HIV viral load. J Natl Med Assoc 1998; 90: 622–4.PubMed
523.
524.
Tateishi T, Krivoruk Y, Ueng Y-F, et al. Identification of human liver cytochrome P-450 3 A4 as the enzyme responsible for fentanyl and sufentanil N-dealkylation. Anesth Analg 1996; 82: 162–72.
525.
Feierman DE, Lasker JM. Metabolism of fentanyl. a synthetic opioid analgesic, by human liver microsomes role of CYP3A4. Drug Metab Dispos 1996; 24: 932–9.
526.
Labroo RB, Thummel KE, Kunze KL, et al. Catalytic role of cytochrome P4503A4 in multiple pathways of alfentanil metabolism. Drug Metab Dispos 1995; 23: 490–6.PubMed
527.
Krivoruk Y, Kinirons MT, Wood AJJ, et al. Alfentanil disposition in vivo is mediated by CYP3A4 in humans. Anesthesiology 1994; 81: A380.CrossRef
528.
Palkama VJ, Isohanni MH, Neuvonen PJ, et al. The effect of intravenous and oral fluconazole on the pharmacokinetics and pharmaco-dynamics of intravenous alfentanil. Anesth Analg 1998; 87: 190–4.PubMed
529.
Foster DJR, Somogyi AA, Bochner F. Methadone N-demethylation in human liver microsomes: lack of steroselectivity and involvement of CYP3A4. Br J Clin Pharmacol 1999; 47: 403–12.CrossRefPubMed
530.
Arlander E, Ekström G, Alm C, et al. Metabolism of ropivacaine in humans is mediated by CYP1A2 and to a minor extent by CYP3 A4: an interaction study with fluvoxamine and ketoconazole as in vivo inhibitors. Clin Pharmacol Ther 1998; 64: 484–91.CrossRefPubMed
531.
Ekström G, Gunnarsson U-B. Ropivacaine. a new amide-type local anesthetic agent, is metabolized by cytochromes P450 1A and 3 A in human liver microsomes. Drug Metab Dispos 1996; 24: 955–61.
532.
Desta Z, Thacker D, Soukhova N, et al. Identification and characterization of human cytochrome P450 (CYP) isoforms interacting with cisapride. Clin Pharmacol Ther 1999; 65: 126.CrossRef
533.
Gotschall RR, Marcucci K, Leeder JS, et al. Cisapride (CIS) bio-transformation: not all CYP3As are created equal. Clin Pharmacol Ther 1999; 65: 127.CrossRef
534.
Wysowski DK, Bacsanyi J. Cisapride and fatal arrhythmia. N Engl Med J 1996; 335: 290–1.CrossRef
535.
Pettignano R, Chambliss R, Darsey E, et al. Cisapride-induced dysrythmia in a pédiatric patient receiving extracorporeal life support. Crit Care Med 1996; 24: 1268–71.CrossRefPubMed
536.
Tiseo PJ, Perdomo CA, Friedhoff LT. Concurrent administration of donepezil HC1 and ketoconazole: assessment of pharmacokinetic changes following single and multiple doses. Br J Clin Pharmacol 1998; 46 Suppl. 1: 30–4.PubMed
537.
Antila S, Honkanen T, Lehtonen L, et al. The CYP3A4 inhibitor itraconazole does not affect the pharmacokinetics of a new calcium-sensitizing drug levosimendan. Int J Clin Pharmacol Ther 1998; 36: 446–9.PubMed
538.
Wienkers LC, Steenwyk RC, Sanders PE, et al. Biotransformation of tirilazad in human: 1. Cytochrome P450 3A-mediated hydrox-ylation of tirilazad mesylate in human liver microsomes. J Pharmacol Exp Ther 1996; 277: 982–90.
539.
Fleishaker JC, Pearson PG, Wienkers LC, et al. Biotransformation of tirilazad in human: 2. Effect of ketoconazole on tirilazad clearance and oral bio availability. J Pharmacol Exp Ther 1996; 277: 991–8.
Metadaten
Titel
Effects of the Antifungal Agents on Oxidative Drug Metabolism
Clinical Relevance
verfasst von
Karthik Venkatakrishnan
Lisa L. von Moltke
Dr David J. Greenblatt
Publikationsdatum
01.02.2000
Verlag
Springer International Publishing
Erschienen in
Clinical Pharmacokinetics / Ausgabe 2/2000
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI
https://doi.org/10.2165/00003088-200038020-00002