Summary
The macrolide antibiotics include natural members, prodrugs and semisynthetic derivatives. These drugs are indicated in a variety of infections and are often combined with other drug therapies, thus creating the potential for pharmacokinetic interactions.
Macrolides can both inhibit drug metabolism in the liver by complex formation and inactivation of microsomal drug oxidising enzymes and also interfere with microorganisms of the enteric flora through their antibiotic effects. Over the past 20 years, a number of reports have incriminated macrolides as a potential source of clinically severe drug interactions. However, differences have been found between the various macrolides in this regard and not all macrolides are responsible for drug interactions. With the recent advent of many semisynthetic macrolide antibiotics it is now evident that they may be classified into 3 different groups in causing drug interactions. The first group (e.g. troleandomycin, erythromycins) are those prone to forming nitrosoalkanes and the consequent formation of inactive cytochrome P450-metabolite complexes. The second group (e.g. josamycin, flurithromycin, roxithromycin, clarithromycin, miocamycin and midecamycin) form complexes to a lesser extent and rarely produce drug interactions. The last group (e.g. spiramycin, rokitamycin, dirithromycin and azithromycin) do not inactivate cytochrome P450 and are unable to modify the pharmacokinetics of other compounds.
It appears that 2 structural factors are important for a macrolide antibiotic to lead to the induction of cytochrome P450 and the formation in vivo or in vitro of an inhibitory cytochrome P450-iron-nitrosoalkane metabolite complex: the presence in the macrolide molecules of a non-hindered readily accessible N-dimethylamino group and the hydrophobic character of the drug.
Troleandomycin ranks first as a potent inhibitor of microsomal liver enzymes, causing a significant decrease of the metabolism of methylprednisolone, theophylline, carbamazepine, phenazone (antipyrine) and triazolam. Troleandomycin can cause ergotism in patients receiving ergot alkaloids and cholestatic jaundice in those taking oral contraceptives.
Erythromycin and its different prodrugs appear to be less potent inhibitors of drug metabolism. Case reports and controlled studies have, however, shown that erythromycins may interact with theophylline, carbamazepine, methylprednisolone, warfarin, cyclosporin, triazolam, midazolam, alfentanil, disopyramide and bromocriptine, decreasing drug clearance. The bioavailability of digoxin appears also to be increased by erythromycin in patients excreting high amounts of reduced digoxin metabolites, probably due to destruction of enteric flora responsible for the formation of these compounds. These incriminated macrolide antibiotics should not be administered concomitantly with other drugs known to be affected metabolically by them, or at the very least, combined administration should be carried out only with careful patient monitoring.
Josamycin, midecamycin and probably also the related compounds miocamycin, clarithromycin and flurithromycin, may have a clinically significant interaction with carbamazepine and cyclosporin, requiring close monitoring. Roxithromycin interaction with drugs such as theophylline or cyclosporin does not seem to justify a dosage reduction. No pharmacokinetic interactions have yet been described for spiramycin, rokitamycin, dirithromycin and azithromycin.
Similar content being viewed by others
References
Albin H, Vincon G, Pehourcq F, Dangoumau J. Influence de la josamycine sur la pharmacocinétique de la carbamazepine. Thérapie 37: 151–157, 1982
Aoki FY, Yatscoff R, Jeffery J, Rush D, Sitar D. Effects of erythromycin on cyclosporine A kinetics in renal transplant patients. Clinical Pharmacology and Therapeutics 41: 221, 1987
Ayanian JZ, Fuchs CS, Stone RM. Lovastatin and rhabdomyolysis. Annals of Internal Medicine 109: 682–683, 1988
Azanza J, Catalan M, Alvarez P, Honorato J, Herreros J, et al. Possible interaction between cyclosporine and josamycin. Journal of Heart Transplantation 9: 265–266, 1990
Azria M, Kiechel JR, Lavenne D. Contribution à l’étude de l’interaction de la triacelyloléandomycine avec l’ergotamine ou la dihydroergotamine. Journal de Pharmacologie 10: 431–438, 1979
Bachmann K. Screening for the influence of host factors on warfarin clearance using a single dose single sample procedure. International Journal of Clinical Pharmacology, Therapy and Toxicology 24: 167–170, 1986
Bachmann K, Nunlee M, Martin M, Sullivan T, Jauregui L, et al. Changes in the steady-state pharmacokinetics of theophylline during treatment with dirithromycin. Journal of Clinical Pharmacology 30: 1001–1005, 1990
Bachmann K, Schwartz JI, Forney Jr R, Frogameni A, Jauregui LE. The effect of erythromycin on the disposition kinetics of warfarin. Pharmacology 28: 171–176, 1984a
Bachmann K, Schwartz JI, Forney Jr R, Jauregui LE. Single dose phenytoin clearance during erythromycin treatment. Research Communications in Chemical Pathology and Pharmacology 4: 207–217, 1984b
Bacourt F, Couffinhal JC. Ischémie des membres par association dihydroergotamine-triacetyloléandomycin. Nouvelle Presse Médicale 7: 1956, 1978
Baldit C, Vincon G, Bistue C, Alin H. Influence d’un nouveau macrolide, la dirithromycine, sur la clairance de l’antipyrine. Thérapie 42: 263–266, 1987
Bandera M, Fioretti M, Rimoldi R, Lazzarini A, Anelli M. Roxithromycin and controlled release theophylline, an interaction study. Chemioterapia 7: 313–316, 1988
Bartkowski RR, Goldberg ME, Larijani GE, Boerner T. Inhibition of alfentanyl metabolism by erythromycin. Clinical Pharmacology and Therapeutics 46: 99–102, 1989
Bartle WR. Possible warfarin-erythromycin interaction. Archives of Internal Medicine 140: 985–987, 1980
Bartolucci L, Gradoli C, Vincenzi V, Iapadre M, Valori C. Macrolide antibiotics and serum theophylline levels in relation to the severity of respiratory impairment: a comparison between the effects of erythromycin and josamycin. Chemioterapia 3: 286–290, 1984
Barzaghi N, Gatti G, Crema F, Faja A, Monteleone M, et al. Effect of flurithromycin, a new macrolide antibiotic, on carbamazepine disposition in normal subjects. International Journal of Clinical and Pharmacological Research 8: 101–105, 1988
Belgian Centre for Drug Supervision. Levertoxiciteit van troleandomycin en oestrogenen. Folia Pharmaceutica (Brussels) 6: 64, 1979
Berrettini WH. A case of erythromycin-induced carbamazepine toxicity. Journal of Clinical Psychiatry 47: 147, 1986
Billaud EM, Guillemain R, Fortineau N, Kitzis M-D, Dreyfus G, et al. Interaction between roxithromycin and cyclosporin in heart transplant patients. Clinical Pharmacokinetics 19: 499–502, 1990
Birmele B, Lebranchu Y, Beliveau F, Rateau H, Fure TY, et al. Absence of interaction between cyclosporine and spiramycin. Transplantation 47: 927–928, 1989
Branigan TA, Robbins RA, Cady WJ, Nickols GC, Ueda CT. The effects of erythromycin on the absorption and disposition of kinetics of theophylline. European Journal of Clinical Pharmacology 21: 115–120, 1981
Brazier JL, Kofman J, Faucon G, Perin-Fayolle M, Lepape A, et al. Retard d’elimination de la théophylline dû à la troléandomycine. Absence d’effect de la josamycine. Thérapie 35: 545–549, 1980
Cadot R, Simonet R, Andre P, Ponchon A, Lombard JY, et al. Absence d’influence de la josamycine sur la pharmacocinétique de l’antipyrine. Thérapie 39: 431–433, 1984
Carranco E, Kareus J, Co S, Peak V, Al-Rajeh S. Carbamazepine toxicity induced by concurrent erythromycin therapy. Archives of Neurology 42: 187–188, 1985
Cazzola M, Matera MG, Paterno E, Scaglione F, Santangelo G, et al. Impact of rokitamycin, a new 16-membered macrolide, on serum theophylline. Journal of Chemotherapy 3: 240–244, 1991
Claudel S, Euvrard P, Borx R, Chavaillon A, Paliard P. Cholestase intrahépatique après association triacetyloléandomycine-estroprogestatif. Nouvelle Presse Medicale 8: 1182–1183, 1979
Couet W, Ingrand I, Reigner B, Grault J, Bizouard J, et al. Lack of effect of ponsinomycin on the plasma pharmacokinetics of theophylline. European Journal of Clinical Pharmacology 37: 101–104, 1989
Couet W, Istin B, Ingrand L, Girault J, Fourtillan JB. Effects of ponsinomycin single-dose kinetics and metabolism of carbamazepine. Therapeutic Drug Monitoring 12: 144–149, 1990a
Couet W, Istin B, Seniuta P, Morel D, Potaux L, et al. Effect of ponsinomycin on cyclosporin pharmacokinetics. European Journal of Clinical Pharmacology 39: 165–167, 1990b
Cummings LH, Kozak Jr PP, Gillman SA. Erythromycin’s effect on theophylline blood levels. Pediatrics 59: 144–145, 1977
Dal Negro R, Turco P, Pomari C, De Conti F. Miocamycin doesn’t affect theophylline serum levels in COPD patients. International Journal of Clinical Pharmacology, Therapy and Toxicology 26: 27–29, 1988
Debruyne D, Jehan A, Bigot MC, Lechavalier B, Prevost JN. Spiramycin has no effect on serum theophylline in asthmatic patients. European Journal of Clinical Pharmacology 30: 505–507, 1986
Delaforge M, Jaouen M, Mansuy D. Dual effects of macrolide antibiotics on rat liver cytochrome P-450 induction and formation of metabolite-complexes: a structure activity relationship. Biochemical Pharmacology 32: 2309–2318, 1983
Delaforge M, Sartori E, Mansuy D. Effects of roxithromycin on rat hepatic P-450 cytochromes: comparison with troleandomycin and erythromycin. British Journal of Clinical Practice 42 (Suppl. 55): 67–69, 1988a
Delaforge M, Sartori E, Mansuy D. In vivo and in vitro effects of a new macrolide antibiotic roxitromycin on rat liver cytochrome P450: comparison with troleandomycin and erythromycin. Chemical-Biological Interactions 68: 179–188, 1988b
Descotes J, Andre P, Evreux JC. Pharmacokinetic drug interactions with macrolide antibiotics. Journal of Antimicrobial Chemotherapy 15: 659–664, 1985
Descotes J, Evreux JC. Drug interactions with spiramycin; lack of influence on antipyrine pharmacokinetics. Chemioterapia 6 (Suppl. 2): 337–338, 1987
Descotes J, Vial T, Delattre D, Evreux JC. Spiramycin: safety in man. Journal of Antimicrobial Chemotherapy 22 (Suppl. B): 207–210, 1988
Dravet C, Mesdjian E, Cenraud B, Roger J. Interaction between carbamazepine and triacetyloleandomycin. Lancet 1: 810–811, 1977a
Dravet C, Mesdjian E, Cenraud B, Roger J. Interaction carbamazepinetroléandomycine: une nouvelle interaction médicamenteuse? Nouvelle Presse Médicale 6: 567–569, 1977b
Fernandes PB. The macrolide revival: thirty-five years after erythromycin. Antimicrobial Newsletter 4: 25–33, 1987
Fevery J, Van Steenbergen W, Desmet V, Deruyttere M, De Groote J. Severe intrahepatic cholestasis due to the combined intake or oral contraceptives and triacetyloleandomycin. Acta Clinica Belgica 38: 242–245, 1983
Fox JL. Infectious asthma treated with triacetyloleandomycin. Pennsylvania Medical Journal 64: 634–635, 1961
Franco A, Boulard P, Massot C, Lecoeur J, Guidicelli H, et al. Ergotamine par association dihydroergotamine-triacetyloléandomycin. Nouvelle Presse Médicale 7: 205, 1978
Franklin MR. Inhibition of mixed-function oxidations by substrates forming reduced cytochrome P-450 metabolic-intermediate complexes. Pharmacology and Therapeutics 2: 227–245, 1977
Fraser DG. Selection of an oral erythromycin product. American Journal of Hospital Pharmacy 37: 1199–11205, 1980
Freeman DJ, Laupacis A, Keown PA, Stiller CR, Carruthers SG. Evaluation of cyclosporine-phenytoin interaction with observations on cyclosporine metabolites. British Journal of Clinical Pharmacology 18: 887–893, 1984
Freeman DJ, Martell R, Carruthers SG, Henrichs D, Keown PA, et al. Cyclosporin-erythromycin interaction in normal subjects. British Journal of Clinical Pharmacology 23: 776–778, 1987
Friedman HW, Bonventre MV. Erythromycin induced digoxin toxicity. Chest 82: 202, 1982
Gascon MP, Dayer P, Waldvogel F. Les interactions médicamenteuses du midazolam. Schweizerische Medizinische Wochenschrift 119: 1834–1836, 1989
Goulden KJ, Camfield P, Dooley JM, Fraser A, Meek DC, et al. Severe carbamazepine intoxication after coadministration of erythromycin. The Journal of Pediatrics 109: 135–138, 1986
Grau E, Fontcuberta J, Felez J. Erythromycin-oral anticoagulants interaction. Archives of Internal Medicine 146: 1639, 1986
Green JA, Clementi WA. Decrease in theophylline clearance after the administration of erythromycin to a patient with obstructive lung disease. Drug Intelligence and Clinical Pharmacy 17: 370–372, 1983
Grino JM, Sabate I, Castelao AM, Guardia M, Seron D, et al. Erythromycin and cyclosporine. Annals of Internal Medicine 105: 467–468, 1986
Guengerich FP, Dannan GA, Wright ST, Martin MV, Kaminsky LS. Purification and characterization of liver microsomal cytochrome P-450: electrophoretic, spectral, catalytic, and immunochemical properties and inducibility of eight isozymes isolated from rats treated with phenobarbital or beta-naphtoflavone. Biochemistry 21: 6019–6030, 1982
Guillemain R, Billaud E, Dreyfus G, Amrein C, Kitzis M, et al. The effects of spiramycin on plasma cyclosporin a concentrations in heart transplant patients. European Journal of Clinical Pharmacology 36: 97–98, 1989.
Gupta SK, Bakran A, Johnson RWG, Rowland M. Cyclosporin-erythromycin interaction in renal transplant patients. British Journal of Clinical Pharmacology 27: 475–481, 1989
Haber I, Hubens H. Cholestatic jaundice after triacetyloleandomycin and oral contraceptives: the diagnostic value of gamma-glutamyl transpeptidase. Acta Gastroenterolica Belgica 43: 475–482, 1980
Halpert J, Naslung B, Betner I. Suicide inactivation of rat liver cytochrome P-450 by chloramphenicol in vivo and in vitro. Molecular Pharmacology 23: 445–452, 1983
Hayton A. Precipitation of acute ergotism by triacetyloleandomycin. New Zealand Medical Journal 69: 42, 1969
Hildebrandt R, Gundert-Remy U, Moller H, Weber E. Lack of clinically important interaction between erythromycin and theophylline. European Journal of Clinical Pharmacology 26: 485–489, 1984
Hildebrandt R, Moller H, Gundert-Remy U. Influence of theophylline on the renal clearance of erythromycin. International Journal of Clinical Pharmacology, Therapy and Toxicology 25: 601–604, 1987
Husserl FE. Erythromycin-warfarin interaction. Archives of Internal Medicine 143: 1831–1836, 1983
Iliopoulou A, Aldhous ME, Johnston A, Turner P. Pharmacokinetic interaction between theophylline and erythromycin. British Journal of Clinical Pharmacology 14: 495–499, 1982
Itkin IH, Menzel ML. The use of macrolide antibiotic substances in the treatment of asthma. Journal of Allergy 45: 146–162, 1970
Jaster PJ, Abbas D. Erythromycin-carbamazepine interaction. Neurology 36: 594–595, 1986
Jensen CWB, Flechner SM, Van Buren CT, Frazier OH, Cooley DA, et al. Exacerbation of cyclosporine toxicity by concomitant administration of erythromycin. Transplantation 43: 263–270, 1987
Jiménez Baos R, Cadórniga Carro R, Moreno Ubeda M, Casado de Frias E. Effects of josamycin on serum levels of theophylline. In Spitzy & Karrer (Eds) Proceedings of the 13th International Congress of Chemotherapy, Vienna, 28 August–2 September, 1983. Vol. 5, pp. 36/61–36/65, Egermann Druckereigesellschaft, 1983
Jonkman JHG, Hendells L. The theophylline erythromycin interaction. Chest 84: 309–310, 1983
Kaplan MA, Godin M. The use of triacetyloleandomycin in chronic infectious asthma. In Welch & Marti-Ibanez (Eds.) Antibiotics Annual 1958–1959, pp. 273–276, New York Inter-science Publishers, New York, 1959
Keller H, Bircher J. Miscellaneous antibiotics. In Dukes MNG (Ed.) Meyler’s side effects of drugs, 9th ed., pp. 452–473, Excerpta Medica, Amsterdam, 1980
Kessler M, Louis J, Renoult E, Vigneron B, Netter P. Interaction between cyclosporin and erythromycin in a kidney transplant patient. European Journal of Clinical Pharmacology 30: 633–634, 1986
Kessler M, Netter P, Zerrouki M, Renoult E, Trechot P, et al. Spiramycin does not increase plasma cyclosporin concentrations in renal transplant patients. European Journal of Clinical Pharmacology 35: 331–332, 1988
Kimelblatt BJ, Slaughter RL. Lack of effect of intravenous erythromycin lactobionate on theophylline clearance. Journal of Allergy and Clinical Immunology 65: 313–314, 1980
Kirst HA, Sides GD. New directions for macrolide antibiotics: structural modifications and in vitro activity. Antimicrobial Agents Chemotherapy 33: 1413–1418, 1989a
Kirst HA, Sides GD. New directions for macrolide antibiotics: pharmacokinetics and clinical efficacy. Antimicrobial Agents Chemotherapy 33: 1419–1422, 1989b
Kozak PP, Cummings LH, Gillman SH. Administration of erythromycin to patients on theophylline. Journal of Allergy and Clinical Immunology 60: 149–151, 1977
Kreft-Jais C, Billaud EM, Gaudry C, Bedrossian J. Effect of josamycin on plasma cyclosporine levels. European Journal of Clinical Pharmacology 32: 327–328, 1987
LaForce CF, Miller MF, Chai H. Effect of erythromycin on theophylline clearance in asthmatic children. Journal of Pediatrics 99: 153–156, 1981
LaForce CF, Szefler SJ, Miller MF, Ebling W, Brenner M. Inhibition of methylprednisolone elimination in the presence of erythromycin therapy. Journal of Allergy and Clinical Immunology 72: 34–39, 1983
Larcan A. L’ergotisme thérapeutique. Journal of Pharmacology 10: 413–430, 1979
Larrey D, Funck-Brentano C, Breil P, Vitaux J, Theodore C, et al. Effects of erythromycin on hepatic drug-metabolizing enzymes in humans. Biochemical Pharmacology 32: 1063–1068, 1983
Lavarenne J, Paire M, Talon O. Influence d’un nouveau macrolide, la midecamycine, sur les taux sanguins de théophylline. Therapie 36: 451–456, 1981
Lehtonen L, Lankinen KS, Wikberg R, Rita H, Salmi HA, et al. Hepatic safety of erythromycin acistrate in 1549 patients with respiratory tract or skin infections. Journal of Antimicrobial Chemotherapy 1991: 233–242, 1991
Ludden TM. Pharmacokinetic interactions of the macrolide antibiotics. Clinical Pharmacokinetics 10: 63–79, 1985
Lysz K, Rosenberg JC, Kaplan MP, Migdal S, Sillix D. Interaction of erythromycin with cyclosporine. Transplantation Proceedings 20 (Suppl. 2): 543–548, 1988
MacNab AJ, Robinson JL, Adderly RJ, D’Orsogna L. Heart block secondary to erythromycin-induced carbamazepine toxicity. Pediatrics 80: 951–952, 1987
Maddux MS, Leeds NH, Organek HW, Hasegawa GR, Bauman JL. The effect of erythromycin on theophylline pharmacokinetics at steady state. Chest 81: 563–565, 1982
Martinet M, Kiechel JR. Interaction of dihydroergotamine and triacetyloleandomycin in the minipig. European Journal of Drug Metabolism and Pharmacokinetics 8: 261–267, 1983
Matthews NT, Havill JH. Ergotism with therapeutic doses of ergotamine tartrate. New Zealand Medical Journal 89: 476–477, 1979
Maxwell DL, Gilmour-White SK, Hall MR. Digoxin toxicity due to interaction of digoxin with erythromycin. British Medical Journal 298: 572, 1989
May DC, Jarboe CH, Ellenburg DT, Roe EJ, Karibo J. The effects of erythromycin on theophylline elimination in normal males. Journal of Clinical Pharmacology 22: 125–130, 1982
Melethil S, Dutta A, Ryan PB, Pingleton SK, Kelly SJ. Steady state urinary excretion of theophylline and its metabolites in the presence of erythromycin. Research Communications in Chemical Pathology and Pharmacology 35: 341–344, 1982
Mesdjian E, Dravet C, Cenraud B, Roger J. Carbamazepine intoxication due to triacetyloleandomycin administration in epileptic patients. Epilepsia 21: 489–496, 1980
Meyer B, Muller F, Wessels P, Maree J. A model to detect interactions between roxithromycin and oral contraceptives. Clinical Pharmacology and Therapeutics 47: 671–674, 1990
Miguet JP, Vuitton D, Pessayre D, Allemand H, Metreau JM, et al. Jaundice from troleandomycin and oral contraceptives. Annals of Internal Medicine 92: 434, 1980
Milne RW, Coulthard K, Nation RL, Penna AC, Roberts G, et al. Lack of effect of erythromycin on the pharmacokinetics of single oral doses of phenytoin. British Journal of Clinical Pharmacology 26: 330–333, 1988
Miura T, Iwasaki A, Komory M, Ohi H, Kitada M, et al. Decrease in a constitutive form of cytochrome P-450 by macrolide antibiotics. Journal of Antimicrobial Chemotherapy 24: 551–559, 1989
Murray MD, Brown BK. Theophylline-erythromycin interaction in an infant. Clinical Pharmacy 1: 107–111, 1982
Nelson MV, Berchou RC, Kareti D, Lewitt PA. Pharmacokinetic evaluation of erythromycin and caffeine administered with bromocriptine. Clinical Pharmacology and Therapeutics 47: 694–697, 1990
Niki Y, Nakajima M, Tsukiyama K, Nakagawa Y, Umeki S, et al. Effect of TE-031(A-56268), a new oral macrolide antibiotic, on serum theophylline concentration. Chemotherapy 36: 515–520, 1988
Paire M, Lavarenne J. Interactions médicamenteuses avec les macrolides sur l’activité des microsomes hépatiques. Pathologie et Biologie 30: 535–538, 1982
Parrish RA, Haulman NJ, Burns RM. Interaction of theophylline with erythromycin base in a patient with seizure activity. Pediatrics 72: 828–830, 1983
Paulsen O, Hoglund P, Nilsson L-G, Bengtsson H-I. The interaction of erythromycin with theophylline. European Journal of Clinical Pharmacology. 32: 493–498, 1987
Paulsen O, Nilsson LG, Saint-Salvi B, Manuel C, Lunell E. No effect of roxithromycin on pharmacokinetic or pharmacodynamic properties of warfarin and its enantiomers. Pharmacology and Toxicology 63: 215–220, 1988
Pavesio D, Mora P, Leone L, Moresco V, Girardo G. Interazione macrolidi-teofillina (Esperienze in pediatria). Minerva Pediatrica 41: 323–328, 1989
Periti P, Mazzei T. Pharmacokinetics of roxithromycin in renal and hepatic failure and drug interactions. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 107–112, 1987
Periti P, Mazzei T, Mini E, Novelli A. Clinical pharmacokinetic properties of the macrolide antibiotics: effects of age and various pathophysiological states (part I). Clinical Pharmacokinetics 16: 193–214, 1989a
Periti P, Mazzei T, Mini E, Novelli A. Clinical pharmacokinetic properties of the macrolide antibiotics: effects of age and various pathophysiological states (part II). Clinical Pharmacokinetics 16: 261–282, 1989b
Periti P, Mazzei T, Mini E, Novelli A. Recenti progressi nella chemioterapia antimicrobica orale: la claritromicina. Farmaci e Terapia 7 (Suppl. 1): 5–63, 1990
Pessayre D, Descatoire V, Konstantinova-Mitcheva M, Wandsheer JC, Cobert N, et al. Self induction by triacetyloleandomycin of its own transformation into a metabolite forming a stable 456nm-absorbing complex with cytochrome P-450. Biochemical Pharmacology 30: 553–558, 1981
Pessayre D, Descatoire V, Tinel M, Larrey D. Self-induction by oleandomycin of its own transformation into a metabolite forming an inactive complex with reduced cytochrome P-450: comparison with troleandomycin. Journal of Pharmacology and Experimental Therapeutics 221: 215–221, 1982a
Pessayre D, Larrey D, Vitaux J, Breil P, Belghidi J, et al. Formation of an inactive cytochrome P-450 Fe(II)-metabolite complex after administration of troleandomycin in humans. Biochemical Pharmacology 31: 1699–1704, 1982
Pessayre D, Larrey D, Funck-Brentano C, Benhamou JP. Drug interactions and hepatic toxicity produced by some macrolide antibiotics. Journal of Antimicrobial Chemotherapy 16 (Suppl. H): 181–194, 1985
Pfeifer HJ, Greenblatt DJ, Friedman P. Effects of three antibiotics on theophylline kinetics. Clinical Pharmacology and Therapeutics 26: 36–40, 1979
Phillips JP, Antal EJ, Smith RB. A pharmacokinetic drug interaction between erythromycin and triazolam. Journal of Clinical Psychopharmacology 6: 297–299, 1986
Pingleton SK, Kelly SJ, Ryan PB. Lack of effect of erythromycin on theophylline serum levels. Chest 78: 352, 1980
Prince RA, Wing DS, Weinberger MM, Hendeles LS, Riegelman S. Effect of erythromycin on theophylline kinetics. Journal of Allergy and Clinical Immunology 68: 427–431, 1981
Principi N, Onorato J, Giuliani MG, Vigano A. Effect of miocamycin on theophylline kinetics in children. European Journal of Clinical Pharmacology 31: 701–704, 1987
Ragosta M, Weihl AC, Rosenfeld LE. Potentially fatal interaction between erythromycin and disopyramide. American Journal of Medicine 86: 465–466, 1989
Reisz G, Pingleton SK, Melethil S, Ryan PB. The effect of erythromycin on theophylline pharmacokinetics in chronic bronchitis. American Review of Respiratory Diseases 127: 581–584, 1983
Renton KW, Gray JD, Hung OR. Depression of theophylline elimination by erythromycin. Clinical Pharmacology and Therapeutics 30: 422–426, 1981
Richer C, Mathieu M, Bah H, Thuillex C, Duroux P, et al. Theophylline kinetics and ventilatory flow in bronchial asthma and chronic airflow obstruction: influence of erythromycin. Clinical Pharmacology and Therapeutics 31: 579–586, 1982
Rieder MJ, Spino M. The theophylline-erythromycin interaction. Journal of Asthma 25: 195–204, 1988
Rimoldi R, Bandera M, Fioretti M, Giorcelli R. Miocamycin and theophylline blood levels. Chemioterapia 5: 213–216, 1986
Rollux R, Plottin F, Mingat J, Bessard G. Ictère après association estroprogestatif-troléandomycine, trois observations. Nouvelle Presse Médicale 8: 1694, 1979
Ruff F, Prosper M, Pujet JC. Theophylline et antibiotiques. Therapie 39: 1–6, 1984
Ruff F, Santais MC, Chastagnol D, Huchon G, Durieux P. Macrolide et théophylline: absence d’interaction josamicine-theophylline. Nouvelle Presse Médicale 10: 175, 1981
Saint-Salvi B, Tremblay D, Surjus A, Lefebure MA. A study of the interaction of roxithromycin with theophylline and carbamazepine. Journal of Antimicrobial Chemotherapy 20 (Suppl. B): 121–129, 1987
Sato RI, Gray DR, Brown SE. Warfarin interaction with erythromycin. Archives of Internal Medicine 144: 2413–2414, 1984
Schwartz JI, Bachmann KA. Erythromycin-warfarin interaction. Archives of Internal Medicine 144: 2094, 1984
Selles JPh, Pains G, Jaber H, Bres J, Armando P. Influence of josamycine on theophylline kinetics. In Spitzy & Karrer (Eds) Proceedings of the 13th International Congress of Chemotherapy, Vienna 28 August–2 September 1983. SS 4.4/1-3, pp. 36/15–20, Egermann Druckereigeselschaft, 1983
Spector SL, Katz FH, Farr RS. Troleandomycin: effectiveness in steroid-dependent asthma and bronchitis. Journal of Allergy and Clinical Immunology 54: 367–379, 1974
Stratton MA. Theophylline-erythromycin base interaction: case report and kinetic profile. Clinical Pharmacy 2: 183–186, 1983
Stults BM, Felice-Johnson J, Higbee MD, Hardigan K. Effect of erythromycin stearate on serum theophylline concentration in patients with chronic obstructive lung disease. Southern Medical Journal 76: 714–718, 1983
Sutton A, Pilot MA. Digoxin toxicity and erythromycin. British Medical Journal 298: 1101, 1989
Szefler SJ, Brenner M, Jusko WJ, Spector SL, Fkesgern KA, et al. Dose and time related effect of troleandomycin on methylprednisolone elimination. Clinical Pharmacology and Therapeutics 32: 166–171, 1982a
Szefler SJ, Ellis EF, Brenner M, Rose JQ, Spector SL, et al. Steroid-specific anticonvulsion interaction aspects of troleandomycin-steroid therapy. Journal of Allergy and Clinical Immunology 69: 455–460, 1982b
Szefler SJ, Rose JQ, Ellis EF, Spector SF, Flesher KA, et al. The effect of troleandomycin on methylprednisolone elimination. Journal of Allergy and Clinical Immunology 66: 447–451, 1980
Tinel M, Descatoire V, Larrey D, et al. Effects of clarithromycin on cytochrome P-450: comparison with other macrolides. Journal of Pharmacology and Experimental Therapeutics 250: 746–751, 1989
Turner PV, Renton KW. The interaction between carbamazepine and erythromycin. Canadian Journal Physiology and Pharmacology 67: 582–586, 1989
Vallarino G, Merlini M, Vallarino R. Josamicina e teofillinici nella patologia respiratoria pediatrica. Giornale Italiano di Chemioterapia 29 (Suppl. 1): 129–133, 1982
Vereerstraeten P, Thiry P, Kinnaert P, Toussaint C. Influence of erythromycin on cyclosporine pharmacokinetics. Transplantation 44: 155–156, 1987
Vernillet L, Bertault-Peres P, Berland J, Barradas J, Durand A, et al. Lack of effect of spiramycin on cyclosporin pharmacokinetics. British Journal of Clinical Pharmacology 27: 789–794, 1989
Villa P, Corti F, Guaitani A, Bartosek I, Casacci F, et al. Effects of a new fluorinated macrolide (P-0501A) and other erythromycins on drug metabolizing enzymes in rat liver. Journal of Antibiotics 39: 463–467, 1986a
Villa P, Corti F, Guaitani A, Bartosek I, Casacci F, et al. Effects of in vivo treatment with a new fluorinated macrolide (P-0501A) and other erythromycins on drug clearance and hepatic functions in perfused rat liver. Journal of Antibiotics 39: 839–844, 1986b
Villa P, Sassella D, Corada M, Bartosek I. Toxic effects of erythromycin base, estolate and RU 28965, a new macrolide, on drug metabolizing enzymes in rat liver. 7th International Symposium on Future Trends in Chemotherapy. Tirrenia 26–28 May 1986c
Viluksela M, Hanhijarvi H, Husband FA, Kosma VM, Collan Y, et al. Comparative liver toxicity of various erythromycin derivatives in animals. Journal of Antimicrobial Chemotherapy 21 (Suppl. D): 927, 1988
Vinçon G, Albin H, Demotes-Mainard F, Guyot M, Bistue C, et al. Effects of josamycin on carbamazepine kinetics. European Journal of Clinical Pharmacology 32: 321–323, 1987
Wadhwa NK, Schroeder TJ, O’Flaherty E, Pesce AJ, Myre SA, et al. Interaction between erythromycin and cyclosporine in a kidney and pancreas allograft recipient. Therapeutic Drug Monitoring 9: 123–125, 1987
Warot D, Bergougnan L, Lamiable D, Berlin I, Bensimon G, et al. Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation. European Journal of Clinical Pharmacology 32: 389–393, 1987
Watkins PB, Wrighton SA, Schuetz EG, Maurel P, Guzelian PS. Macrolide antibiotics inhibit the degradation of the glucocorticoid-responsive cytochrome P-450 in rat hepatocytes in vivo and in primary monolayer culture. Journal of Biological Chemistry 261: 6264–6271, 1986
Weibert RT, McQuade Lorentz S, Townsend RJ, Cook CE, Klauber MR, et al. Effect of erythromycin in patients receiving long-term warfarin therapy. Clinical Pharmacy 8: 210–214, 1989
Weinberger M. TAO and theophylline. Hospital Practice 13: 22, 1978
Weinberger M, Hudgel D, Spector S, Chidsey C. Inhibition of theophylline clearance by troleandomycin. Journal of Allergy and Clinical Immunology 59: 228–231, 1977
Wiggins J, Arbab O, Ayres JG, Skinner C. Elevated serum theophylline concentration following cessation of erythromycin treatment. European Journal of Respiratory Disease 68: 298–300, 1986
Wong YY, Ludden TM, Bell RD. Effect of erythromycin on carbamazepine kinetics. Clinical Pharmacology and Therapy 33: 460–464, 1983
Woody RC, Kearns GL, Bolyard KJ. Carbamazepine intoxication following the use of erythromycin in children. Pediatric Infectious Disease Journal 6: 578–579, 1987
Wrighton SA, Maurel P, Schuetz EG, Watkins PB, Young B, et al. Identification of the cytochrome P-450 induced by macrolide antibiotics in rat liver as the glucocorticoid responsive cytochrome P-450p. Biochemistry 24: 2171–2178, 1985
Wroblewski BA, Singer WD, Whyte J. Carbamazepine-erythromycin interaction: case studies and clinical significance. Journal of American Medical Association 255: 1165–1167, 1986
Yee GC, McGuire TR. Pharmacokinetic drug interactions with cyclosporin (Part I). Clinical Pharmacokinetics 19: 319–332, 1990
Yee GC, McGuire TR. Pharmacokinetic drug interactions with cyclosporin (Part II). Clinical Pharmacokinetics 19: 400–415, 1990
Young RA, Gonzalez JP, Sorkin EM. Roxithromycin: a review of its antibacterial activity, pharmacokinetic properties and clinical efficacy. Drugs 37: 8–41, 1989
Zarowitz BJ, Szefler SJ, Lasezkay GM. Effect of erythromycin base on theophylline kinetics. Clinical Pharmacology and Therapeutics 29: 601–605, 1981
Ziger RS, Schatz M, Sperling W, Simon RA, Stevenson DD. Efficacy of troleandomycin in outpatients with severe, corticosteroid-dependent asthma. Journal of Allergy and Clinical Immunology 66: 438, 1980
Zini R, Fournet MP, Barre J, Tremblay D, Tillement JP. In vitro study of roxithromycin binding to serum proteins and erythrocytes in man. British Journal of Clinical Practice 42 (Suppl. 5): 54, 1987
Author information
Authors and Affiliations
Additional information
An erratum to this article is available at http://dx.doi.org/10.1007/BF03259381.
Rights and permissions
About this article
Cite this article
Periti, P., Mazzei, T., Mini, E. et al. Pharmacokinetic Drug Interactions of Macrolides. Clin-Pharmacokinet 23, 106–131 (1992). https://doi.org/10.2165/00003088-199223020-00004
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-199223020-00004