nach oben

Clinical Pharmacokinetics

Erschienen in:

01.07.2008 | Review Article

Pharmacokinetic Comparison of the Potential Over-the-Counter Statins Simvastatin, Lovastatin, Fluvastatin and Pravastatin

verfasst von: Dr Pertti J. Neuvonen, Janne T. Backman, Mikko Niemi

Erschienen in: Clinical Pharmacokinetics | Ausgabe 7/2008

Einloggen, um Zugang zu erhalten

Abstract

HMG-CoA reductase inhibitors (statins) dose-dependently lower both the level of low-density lipoprotein cholesterol and risk of cardiovascular disease. In 2004, the UK approved a low-dose over-the-counter (OTC) simvastatin, but the US has rejected applications for non-prescription preparations of statins. The pharmacokinetics and interaction potentials of the possible OTC candidate statins simvastatin, lovastatin, fluvastatin and pravastatin are clearly different. Simvastatin and lovastatin are mainly metabolized by cytochrome P450 (CYP) 3A, fluvastatin is metabolized by CYP2C9, and pravastatin is excreted largely unchanged. Several cell membrane transporters can influence the disposition of statins, e.g. the organic anion transporting polypeptide (OATP) 1B1 enhances their hepatic uptake. The c.521T>C (p.Vall74Ala) genetic polymorphism of SLCO1B1 (encoding OATP1B1) considerably increases the plasma concentrations of simvastatin acid and moderately increases those of pravastatin but seems to have no significant effect on fluvastatin. Strong inhibitors of CYP3A (itraconazole, ritonavir) greatly (up to 20-fold) increase plasma concentrations of simvastatin, lovastatin and their active acid forms, thus enhancing the risk of myotoxicity. Weak or moderately potent CYP3A inhibitors such as verapamil, diltiazem and grapefruit juice can be used cautiously with low doses of simvastatin or lovastatin, but their concomitant use needs medical supervision. Potent inducers of CYP3A can greatly decrease plasma concentrations of simvastatin and simvastatin acid, and probably those of lovastatin and lovastatin acid. Although fluvastatin is metabolized by CYP2C9, its concentrations are changed less than 2-fold by inhibitors or inducers of CYP2C9. Pravastatin plasma concentrations are not significantly affected by any CYP inhibition and only slightly affected by inducers. Ciclosporin inhibits CYP3A, P-glycoprotein and OATP1B1. Gemfibrozil and its glucuronide inhibit CYP2C8 and OATP1B1. Ciclosporin and gemfibrozil increase plasma concentrations of statins and the risk of their myotoxicity, but fluvastatin seems to carry a smaller risk than other statins. Inhibitors of OATP1B1 may decrease the benefit-risk ratio of simvastatin, lovastatin and pravastatin by interfering with their (active acid forms) entry into hepatocytes. Understanding the differences in the pharmacokinetics and interaction potential of various statins helps in their selection for possible non-prescription status. On the pharmacokinetic basis, fluvastatin and pravastatin can be better choices than simvastatin or lovastatin for an OTC statin.

Scandinavian Simvastatin Survival Study Group. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet 1994; 344: 1383–9

Bays H. Statin safety: an overview and assessment of the data — 2005. Am J Cardiol 2006; 97 Suppl.: 6C–26CPubMedCrossRef

Jones P, Kafonek S, Laurora I, et al. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin, and fluvastatin in patients with hypercholesterolemia (the CURVES study). Am J Cardiol 1998; 81: 582–7PubMedCrossRef

OTC statins: a bad decision for public health [editorial]. Lancet 2004; 363: 1659CrossRef

Gotto AM. Over-the-counter statins and cardiovascular disease prevention: perspectives, challenges, and opportunities. Clin Pharmacol Ther 2005; 78: 213–7PubMedCrossRef

Strom BL. Statins and over-the-counter availability. N Engl J Med 2005; 352: 1403–5PubMedCrossRef

Davidoff F. Primary prevention with over-the-counter statins: a cautionary tale. Clin Pharmacol Ther 2005; 78: 218–20PubMedCrossRef

Rashid S. Should cholesterol-lowering medications be available in Canada without a prescription. Can J Cardiol 2007; 23: 189–93PubMedCrossRef

Gotto AM. Is it appropriate to make statins available over the counter? Over-the-counter statins are worth considering in primary prevention of cardiovascular disease. Circulation 2006; 114: 1310–4PubMedCrossRef

10.

Barter PJ, Rye KA. Is it appropriate to make statins available over the counter? The argument against the appropriateness of over-the-counter statins. Circulation 2006; 114: 1315–20PubMedCrossRef

11.

Lennernäs H, Fager G. Pharmacodynamics and pharmacokinetics of the HMG-CoA reductase inhibitors: similarities and differences. Clin Pharmacokinet 1997; 32: 403–25PubMedCrossRef

12.

Hamelin BA, Turgeon J. Hydrophilicity/lipophilicity: relevance for the pharmacology and clinical effects of HMG-CoA reductase inhibitors. Trends Pharmacol Sci 1998; 19: 26–37PubMedCrossRef

13.

Sirtori CR. Tissue selectivity of hydroxymethylglutaryl coenzyme A (HMG CoA) reductase inhibitors. Pharmacol Ther 1993; 60: 431–59PubMedCrossRef

14.

Schectman G, Hiatt J. Dose-response characteristics of cholesterol-lowering drug therapies: implications for treatment. Ann Intern Med 1996; 125: 990–1000PubMed

15.

Chen C, Mireles RJ, Campbell SD, et al. Differential interaction of 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors with ABCB1, ABCC2, and OATP1B1. Drug Metab Dispos 2005; 33: 537–46PubMedCrossRef

16.

Shitara Y, Sugiyama Y. Pharmacokinetic and pharmacodynamic alterations of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors: drug-drug interactions and interindividual differences in transporter and metabolic enzyme functions. Pharmacol Ther 2006; 112: 71–105PubMedCrossRef

17.

Neuvonen PJ, Niemi M, Backman JT. Drug interactions with lipid-lowering drugs: mechanisms and clinical relevance. Clin Pharmacol Ther 2006; 80: 565–81PubMedCrossRef

18.

Scripture CD, Pieper JA. Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet 2001; 40: 263–81PubMedCrossRef

19.

Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol 2005; 19: 117–26PubMedCrossRef

20.

Singhvi SM, Pan HY, Morrison RA, et al. Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. Br J Clin Pharmacol 1990; 29: 239–43PubMedCrossRef

21.

Hatanaka T. Clinical pharmacokinetics of pravastatin: mechanisms of pharmacokinetic events. Clin Pharmacokinet 2000; 39: 397–412PubMedCrossRef

22.

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: 332–41PubMedCrossRef

23.

Kivistö KT, Kantola T, Neuvonen PJ. Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 1998; 46: 49–53PubMedCrossRef

24.

Niemi M, Pasanen MK, Neuvonen PJ. SLCO1B1 polymorphism and sex affect the pharmacokinetics of pravastatin but not of fluvastatin. Clin Pharmacol Ther 2006; 80: 356–66PubMedCrossRef

25.

Pasanen MK, Neuvonen M, Neuvonen PJ, et al. SLCO1B1 polymorphism markedly affects the pharmacokinetics of simvastatin acid. Pharmacogenet Genomics 2006; 16: 873–9PubMedCrossRef

26.

Kirchheiner J, Kudlicz D, Meisel C, et al. Influence of CYP2C9 polymorphisms on the pharmacokinetics and cholesterol-lowering activity of (−)-3S,5R-fluvastatin and (+)-3R,5S-fluvastatin in healthy volunteers. Clin Pharmacol Ther 2003; 74: 186–94PubMedCrossRef

27.

Kim KA, Park PW, Lee OJ, et al. Effect of polymorphic CYP3A5 genotype on the single-dose simvastatin pharmacokinetics in healthy subjects. J Clin Pharmacol 2007; 47: 87–93PubMedCrossRef

28.

Lilja JJ, Kivistö KT, Neuvonen PJ. Grapefruit-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998; 64: 477–83PubMedCrossRef

29.

Kantola T, Kivistö KT, Neuvonen PJ. Erythromycin and verapamil considerably increase serum simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 1998; 64: 177–82PubMedCrossRef

30.

Lilja JJ, Neuvonen M, Neuvonen PJ. Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004; 58: 56–60PubMedCrossRef

31.

Lilja JJ, Kivistö KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP 3A4 substrate simvastatin. Clin Pharmacol Ther 2000; 68: 384–90PubMedCrossRef

32.

Kantola T, Backman JT, Niemi M, et al. Effect of fluconazole on plasma fluvastatin and pravastatin concentrations. Eur J Clin Pharmacol 2000; 56: 225–9PubMedCrossRef

33.

Backman JT, Kyrklund C, Kivistö KT. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 2000; 68: 122–9PubMedCrossRef

34.

Kyrklund C, Backman JT, Kivistö KT, et al. Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Clin Pharmacol Ther 2001; 69: 340–5PubMedCrossRef

35.

Kyrklund C, Backman JT, Kivistö KT, et al. Rifampin greatly reduces plasma simvastatin and simvastatin acid concentrations. Clin Pharmacol Ther 2000; 68: 592–7PubMedCrossRef

36.

Kyrklund C, Backman JT, Neuvonen M, et al. Effect of rifampicin on pravastatin pharmacokinetics in healthy subjects. Br J Clin Pharmacol 2004; 57: 181–7PubMedCrossRef

37.

Kyrklund C, Backman JT, Neuvonen M, et al. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther 2003; 73: 538–44PubMedCrossRef

38.

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: 1191–9PubMed

39.

Prueksaritanont T, Ma B, Yu N. The human hepatic metabolism of simvastatin hydroxyl acids is mediated primarily by CYP3A, and not CYP2D6. Br J Clin Pharmacol 2003; 56: 120–4PubMedCrossRef

40.

Matsushima S, Maeda K, Kondo C, et al. Identification of the hepatic efflux transporters of organic anions using double-transfected Madin-Darby canine kidney II cells expressing human organic anion-transporting polypeptide 1B1 (OATP1B1)/multidrug resistance-associated protein 2, OATP1B1/multidrug resistance 1, and OATP1B1/breast cancer resistance protein. J Pharmacol Exp Ther 2005; 314: 1059–67PubMedCrossRef

41.

Ho RH, Kim RB. Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther 2005; 78: 260–77PubMedCrossRef

42.

Niemi M. Role of OATP transporters in the disposition of drugs. Pharmacogenomics 2007; 8: 787–802PubMedCrossRef

43.

Tirona RG. Ethnic differences in statin disposition. Clin Pharmacol Ther 2005; 78: 311–6PubMedCrossRef

44.

Sakaeda T, Fujino H, Komoto C, et al. Effect of acid and lactone forms of eight HMG-CoA reductase inhibitors on CYP-mediated metabolism and MDR1-mediated transport. Pharmaceut Res 2006; 23: 506–12CrossRef

45.

Wang E, Casciano CN, Clement RP, et al. HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors of P-glycoprotein. Pharmaceut Res 2001; 18: 800–6CrossRef

46.

Parker TS, McNamara DJ, Brown C, et al. Mevalonic acid in human plasma: relationship of concentration and circadian rhythm to cholesterol synthesis rates in man. Proc Natl Acad Sci U S A 1982; 79: 3037–41PubMedCrossRef

47.

Plakogiannis R, Cohen H. Optimal low-density lipoprotein cholesterol lowering: morning versus evening statin administration. Ann Pharmacother 2007; 41: 106–10PubMed

48.

Wang RW, Kari PH, Lu AY, 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: 355–61PubMedCrossRef

49.

Christians U, Jacobsen W, Floren LC. Metabolism and drug interactions of 3-hydroxy-methylglutaryl coenzyme A reductase inhibitors in transplant patients: are the statins mechanistically similar? Pharmacol Ther 1998; 80: 1–34PubMedCrossRef

50.

Nakai D, Nakagomi R, Furuta Y, et al. Human liver-specific organic anion transporter, LST-1, mediates uptake of pravastatin by human hepatocytes. J Pharmacol Exp Ther 2001; 297: 861–7PubMed

51.

Koga T, Shimada Y, Kuroda M, et al. Tissue-selective inhibition of cholesterol synthesis in vivo by pravastatin sodium, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Biochim Biophys Acta 1990; 1045: 115–20PubMedCrossRef

52.

Buckett L, Davidson R, Dunkley C, et al. Selectivity of ZD4522 for inhibition of cholesterol synthesis in hepatic versus non-hepatic cells [abstract]. Atherosclerosis 2000; 151: 41CrossRef

53.

Shitara Y, Sato H, Sugiyama Y. Evaluation of drug-drug interaction in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 2005; 45: 689–723PubMedCrossRef

54.

Kivistö KT, Niemi M. Influence of drug transporter polymorphisms on pravastatin pharmacokinetics in humans. Pharmaceut Res 2007; 24: 239–47CrossRef

55.

Mangravite LM, Thorn CF, Kraus RM. Clinical implications of pharmacogenomics of statin treatment. Pharmacogenom J 2006; 6: 360–74CrossRef

56.

Kivistö KT, Niemi M, Schaeffeler E, et al. Lipid-lowering response to statins is affected by CYP3A5 polymorphism. Pharmacogenetics 2004; 14: 523–5PubMedCrossRef

57.

Nishizato Y, Ieiri I, Suzuki H, et al. Polymorphisms of OATP-C (SLC21A6) and OAT3 (SLC22A8) genes: consequences for pravastatin pharmacokinetics. Clin Pharmacol Ther 2003; 73: 554–65PubMedCrossRef

58.

Mwinyi J, Johne A, Bauer S, et al. Evidence for inverse effects of OATP-C (SLC21A6) 5 and 1b haplotypes on pravastatin kinetics. Clin Pharmacol Ther 2004; 75: 415–21PubMedCrossRef

59.

Niemi M, Schaeffeler E, Lang T, et al. High plasma pravastatin concentrations are associated with single nucleotide polymorphisms and haplotypes of organic anion transporting polypeptide-C (OATP-C, SLCO1B1). Pharmacogenetics 2004; 14: 429–40PubMedCrossRef

60.

Kim RB. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) and genetic variability (single nucleotide polymorphism) in a hepatic drug uptake transporter: what’s it all about? Clin Pharmacol Ther 2004; 75: 381–5PubMedCrossRef

61.

Niemi M, Arnold KA, Backman JT, et al. Association of genetic polymorphism in ABCC2 with hepatic MRP2 expression and pravastatin pharmacokinetics. Pharmacogenet Genomics 2006; 16: 801–8PubMedCrossRef

62.

Pasanen MK, Neuvonen PJ, Niemi M. Global analysis of genetic variation in SLCO1B1. Pharmacogenomics 2008; 65: 78–86

63.

Tachibana-Iimori R, Tabara Y, Kusuhara H, et al. Effect of genetic polymorphism of OATP-C (SLCO1B1) on lipid-lowering response to HMG-CoA reductase inhibitors. Drug Metab Pharmacokinet 2004; 19: 375–80PubMedCrossRef

64.

Niemi M, Neuvonen PJ, Hofmann U, et al. Acute effects of pravastatin on cholesterol synthesis are associated with SLCO1B1 (encoding OATP1B1) haplotype *17. Pharmacogenet Genomics 2005; 15: 303–9PubMedCrossRef

65.

Neuvonen PJ, Jalava M. Itraconazole drastically increases plasma concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1996; 60: 54–61PubMedCrossRef

66.

Jacobson TA. Comparative interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 2004; 94: 1140–6PubMedCrossRef

67.

Fichtenbaum CJ, Gerber JG, Rosenkranz SL, et al. Pharmacokinetic interactions between protease inhibitors and statins in seronegative volunteers: ACTG study A5047. AIDS 2002; 16: 569–77PubMedCrossRef

68.

Mazzu AL, Lasseter KC, Shamblen EC, et al. Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 2000; 68: 391–400PubMedCrossRef

69.

Azie NE, Brater DC, Becker PA, et al. The interaction of diltiazem with lovastatin and pravastatin. Clin Pharmacol Ther 1998; 64: 369–77PubMedCrossRef

70.

Mousa O, Brater DC, Sunblad KJ, et al. The interaction of diltiazem with simvastatin. Clin Pharmacol Ther 2000; 67: 267–74PubMedCrossRef

71.

Watanabe H, Kosuge K, Nishio S, et al. Pharmacokinetic and pharmacodynamic interactions between simvastatin and diltiazem in patients with hypercholesterolemia and hypertension. Life Sci 2004; 76: 281–92PubMedCrossRef

72.

Becquemont L, Neuvonen M, Verstuyft C, et al. Amiodarone interacts with simvastatin but not with pravastatin disposition kinetics. Clin Pharmacol Ther 2007; 81: 679–84PubMedCrossRef

73.

Hedman M, Neuvonen PJ, Neuvonen M, et al. Pharmacokinetics and pharmacodynamics of pravastatin in pediatric and adolescent cardiac transplant recipients on a regimen of triple immunosuppression. Clin Pharmacol Ther 2004; 75: 101–9PubMedCrossRef

74.

Regazzi MB, Iacona I, Campana C, et al. Altered disposition of pravastatin following concomitant drug therapy with cyclosporin A in transplant recipients. Transplant Proc 1993; 25: 2732–4PubMed

75.

Åsberg A. Interactions between cyclosporin and lipid-lowering drugs: implications for organ transplant recipients. Drugs 2003; 63: 367–78PubMedCrossRef

76.

Park JW, Siekmeier R, Lattke P, et al. Pharmacokinetics and pharmacodynamics of fluvastatin in heart transplant recipients taking cyclosporine A. J Cardiovasc Pharmacol Ther 2001; 6: 351–61PubMedCrossRef

77.

Transon C, Leemann 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: 209–15PubMedCrossRef

78.

Spence JD, Munoz CE, Hendricks L, et al. Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol 1995; 76: 80A–83APubMedCrossRef

79.

Kantola T, Kivistö KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1998; 63: 397–402PubMedCrossRef

80.

Lilja JJ, Kivistö KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999; 66: 118–27PubMed

81.

Fukazawa I, Uchida N, Uchida E, et al. Effects of grapefruit juice on pharmacokinetics of atorvastatin and pravastatin in Japanese. Br J Clin Pharmacol 2004; 57: 448–55PubMedCrossRef

82.

Ucar M, Neuvonen M, Luurila H, et al. Carbamazepine markedly reduces serum concentrations of simvastatin and simvastatin acid. Eur J Clin Pharmacol 2004; 59: 879–82PubMedCrossRef

83.

Sugimoto R, Ohmori M, Tsuruoka S, et al. Different effects of St John’s wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001; 70: 518–24PubMedCrossRef

84.

Schmassmann-Suhijar D, Bullingham R, Gasser R, et al. Rhabdomyolysis due to interaction of simvastatin with mibefradil [letter]. Lancet 1998; 351: 1929–30PubMedCrossRef

85.

Lees RS, Lees AM. Rhabdomyolysis from the coadministration of lovastatin and the antifungal agent itraconazole [letter]. N Engl J Med 1995; 333: 664–5PubMedCrossRef

86.

Andreou ER, Ledger S. Potential drug interaction between simvastatin and danazol causing rhabdomyolysis. Can J Clin Pharmacol 2003; 10: 172–4PubMed

87.

Jacobson RH, Wang P, Glueck CJ. Myositis and rhabdomyolysis associated with concurrent use of simvastatin and nefazodone. JAMA 1997; 277: 296–7PubMedCrossRef

88.

Gladding P, Pilmore H, Edwards C. Potentially fatal interaction between diltiazem and statins. Ann Intern Med 2004; 140: W31PubMed

89.

Roten L, Schoenenberger RA, Rrahenbuhl S, et al. Rhabdomyolysis in association with simvastatin and amiodarone. Ann Pharmacother 2004; 38: 978–81PubMedCrossRef

90.

Jamal SM, Eisenberg MJ, Christopoulos S. Rhabdomyolysis associated with hydroxymethylglutaryl-coenzyme A reductase inhibitors. Am Heart J 2004; 47: 956–65CrossRef

91.

Rahri AJ, Valkonen MM, Vuoristo MR, et al. Rhabdomyolysis associated with concomitant use of simvastatin and clarithromycin. Ann Pharmacother 2004; 38: 719

92.

Vlahakos DV, Manginas A, Chilidou D, et al. Itraconazole-induced rhabdomyolysis and acute renal failure in a heart transplant recipient treated with simvastatin and cyclosporine. Transplantation 2002; 73: 1962–4PubMedCrossRef

93.

Molden E, Andersson RS. Simvastatin-associated rhabdomyolysis after coadministration of macrolide antibiotics in two patients. Pharmacotherapy 2007; 27: 603–7PubMedCrossRef

94.

Aboulafia DM, Johnston R. Simvastatin-induced rhabdomyolysis in an HIV-infected patient with coronary artery disease. AIDS Patient Care 2000; 14: 13–8CrossRef

95.

Cheng CH, Miller C, Lowe C, et al. Rhabdomyolysis due to probable interaction between simvastatin and ritonavir. Am J Health Syst Pharm 2002; 59: 728–30PubMed

96.

Granfors MT, Wang JS, Rajosaari LI, et al. Differential inhibition of cytochrome P450 3A4, 3A5 and 3A7 by five human immunodeficiency virus (HIV) protease inhibitors in vitro. Basic Clin Pharmacol Toxicol 2006; 98: 79–85PubMedCrossRef

97.

Fichtenbaum CJ, Gerber JG. Interactions between antiretroviral drugs and drugs used for the therapy of the metabolic complications encountered during HIV infection. Clin Pharmacokinet 2002; 41: 1195–211PubMedCrossRef

98.

Rogers JD, Zhao J, Liu L, et al. Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Clin Pharmacol Ther 1999; 66: 358–66PubMedCrossRef

99.

Dreier JP, Endres M. Statin-associated rhabdomyolysis triggered by grapefruit consumption. Neurology 2004; 62: 670PubMedCrossRef

100.

Bailey DG, Dresser GR. Interactions between grapefruit juice and cardiovascular drugs. Am J Cardiovasc Drugs 2004; 4: 281–97PubMedCrossRef

101.

Wang JS, Neuvonen M, Wen X, et al. Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes. Drug Metab Dispos 2002; 30: 1352–6PubMedCrossRef

102.

Shitara Y, Hirano M, Sato H, et al. Gemfibrozil and its glucuronide inhibit the organic anion transporting polypeptide 2 (OATP2/OATP1B1:SLC21A6)-mediated hepatic uptake and CYP2C8-mediated metabolism of cerivastatin: analysis of the mechanism of the clinically relevant drug-drug interaction between cerivastatin and gemfibrozil. J Pharmacol Exp Ther 2004; 311: 228–36PubMedCrossRef

103.

Ogilvie BW, Zhang D, Li W, et al. Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions. Drug Metab Dispos 2006; 34: 191–7PubMedCrossRef

104.

Murphy MJ, Dominiczak MH. Efficacy of statin therapy: possible effect of phenytoin. Postgrad Med J 1999; 75: 359–60PubMed

105.

Hirano M, Maeda R, Shitara Y, et al. Drug-drug interaction between pravastatin and various drugs via OATP1B1. Drug Metab Dispos 2006; 34: 1229–36PubMedCrossRef

106.

Pan WJ, Gustavson LE, Achari R, et al. Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. J Clin Pharmacol 2000; 40: 316–23PubMedCrossRef

107.

Bergman AJ, Murphy G, Burke J, et al. Simvastatin does not have a clinically significant pharmacokinetic interaction with fenofibrate in humans. J Clin Pharmacol 2004; 44: 1054–62PubMedCrossRef

108.

Graham DJ, Staffa JA, Shatin D, et al. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA 2004; 292: 2585–90PubMedCrossRef

109.

Jones PH, Davidson MH. Reporting rate of rhabdomyolysis with fenofibrate-statin versus gemfibrozil-any statin. Am J Cardiol 2005; 95: 120–2PubMedCrossRef

110.

Law M, Rudnicka AR. Statin safety: a systematic review. Am J Cardiol 2006; 97(8A): 52C–60CPubMedCrossRef

111.

Combalbert J, Fabre I, Fabre G, et al. Metabolism of cyclosporin A: IV. Purification and identification of the rifampicin-inducible human liver cytochrome P-450 (cyclosporin A oxidase) as a product of P450IIIA gene subfamily. Drug Metab Dispos 1989; 17: 197–207PubMed

112.

Arnadottir M, Eriksson LO, Thysell H, et al. Plasma concentration profiles of simvastatin 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Nephron 1993; 65: 410–3PubMedCrossRef

113.

Ichimaru N, Takahara S, Rokado Y, et al. Changes in lipid metabolism and effect of simvastatin in renal transplant recipients induced by cyclosporine or tacrolimus. Atherosclerosis 2001; 158: 417–23PubMedCrossRef

114.

Olbricht C, Wanner C, Eisenhauer T, et al. Accumulation of lovastatin, but not pravastatin, in the blood of cyclosporine-treated kidney graft patients after multiple doses. Clin Pharmacol Ther 1997; 62: 311–21PubMedCrossRef

115.

Omar MA, Wilson JP. FDA adverse event reports on statin-associated rhabdomyolysis. Ann Pharmacother 2002; 36: 288–95PubMedCrossRef

116.

Omar MA, Wilson JP, Cox TS. Rhabdomyolysis and HMG-CoA reductase inhibitors [published erratum appears in Ann Pharmacother 2001; 35: 1296]. Ann Pharmacother 2001; 35: 1096–107PubMedCrossRef

117.

Ballantyne CM, Corsini A, Davidson MH, et al. Risk for myopathy with statin therapy in high-risk patients. Arch Intern Med 2003; 163: 553–64PubMedCrossRef

118.

Tobert JA. Efficacy and long-term adverse effect pattern of lovastatin. Am J Cardiol 1988; 62: 28J–34JPubMedCrossRef

119.

Page 2nd RL, Miller GG, Lindenfeld J. Drug therapy in the heart transplant recipient: part IV. Drug-drug interactions. Circulation 2005; 111: 230–9PubMedCrossRef

120.

Lindenfeld J, Page 2nd RL, Zolty R, et al. Drug therapy in the heart transplant recipient: part III. Common medical problems. Circulation 2005; 111: 113–7PubMedCrossRef

121.

Williams D, Feely J. Pharmacokinetic-pharmacodynamic drug interactions with HMG-CoA reductase inhibitors. Clin Pharmacokinet 2002; 41: 343–70PubMedCrossRef

122.

Tornio A, Pasanen MR, Laitila J, et al. Comparison of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) as inhibitors of cytochrome P450 2C8. Basic Clin Pharmacol Toxicol 2005; 97: 104–8PubMedCrossRef

123.

Andrus MR. Oral anticoagulant drug interactions with statins: case report of fluvastatin and review of the literature. Pharmacotherapy 2004; 24: 285–90PubMedCrossRef

124.

Kim M-J, Nafziger AN, Kashuba ADM, et al. Effects of fluvastatin and cigarette smoking on CYP2C9 activity measured using the probe S-warfarin. Eur J Clin Pharmacol 2006; 62: 431–6PubMedCrossRef

Titel: Pharmacokinetic Comparison of the Potential Over-the-Counter Statins Simvastatin, Lovastatin, Fluvastatin and Pravastatin
verfasst von: Dr Pertti J. Neuvonen
Janne T. Backman
Mikko Niemi
Publikationsdatum: 01.07.2008
Verlag: Springer International Publishing
Erschienen in: Clinical Pharmacokinetics / Ausgabe 7/2008
Print ISSN: 0312-5963
Elektronische ISSN: 1179-1926
DOI: https://doi.org/10.2165/00003088-200847070-00003

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten