The human hepatic metabolism of simvastatin hydroxy acid is mediated primarily by CYP3A, and not CYP2D6

British Journal of Clinical Pharmacology

Volumn 56, Issue 1, 2003, Pages 120-124

  Prueksaritanont, Thomayant ^a   Ma, Bennett ^a   Yu, Nathan ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

CYP2C8; CYP2D6; CYP3A4; CYP3A5; Simvastatin; Simvastatin hydroxy acid

Indexed keywords

ANTIBODY; CYTOCHROME P450 1A2; CYTOCHROME P450 2A6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A; CYTOCHROME P450 3A4; CYTOCHROME P450 3A5; DRUG METABOLITE; ISOENZYME; QUERCETIN; RECOMBINANT ENZYME; SIMVASTATIN; SIMVASTATIN HYDROXYACID; TROLEANDOMYCIN; UNCLASSIFIED DRUG;

AEROBIC METABOLISM; ARTICLE; CATALYSIS; CONCENTRATION (PARAMETERS); CROSS REACTION; DRUG METABOLISM; ENZYME ACTIVITY; HUMAN; HUMAN TISSUE; IMMUNOASSAY; IN VITRO STUDY; LIVER METABOLISM; LIVER MICROSOME; PRIORITY JOURNAL;

ARYL HYDROCARBON HYDROXYLASES; CYTOCHROME P-450 CYP2D6; CYTOCHROME P-450 CYP3A; HUMANS; LIVER; MICROSOMES; OXIDOREDUCTASES, N-DEMETHYLATING; SIMVASTATIN;

EID: 0038336614     PISSN: 03065251     EISSN: None     Source Type: Journal    
DOI: 10.1046/j.1365-2125.2003.01833.x     Document Type: Article

References (12)

1. Prueksaritanont T, Gorham LM, Ma B et al. In vitro metabolism of simvastatin in humans: identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 1997; 25: 1191-1199.
2. Vickers S, Duncan CA, Chen I-W, Rosegay A, Duggan DE. Metabolic disposition studies of simvastatin, a cholesterol-lowering prodrug. Drug Metab Dispos 1990; 18: 138-145.
3. Nordin C, Dahl M-L, Eriksson M, Sjoberg S. Is the cholesterol-lowering effect of simvastatin influenced by CYP2D6 polymorphism. Lancet 1997; 350: 29-30.
4. Mulder AB, van Liif HJ, Bon MAM et al. Association of polymorphism in the cytochrome CYP2D6 and the efficacy and tolerability of simvastatin. Clin Pharmacol Ther 2001; 70: 546-551.
5. Prueksaritanont T, Zhao J, Ma B et al. Mechanistic studies on the metabolic interactions between gemfibrozil and statins. J Pharmacol Exp Ther 2002; 301: 1042-1051.
6. 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: 332-341.
7. Newton DJ, Wang RW, Lu AHY. Cytochrome P450 inhibitors: evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 1995; 23: 154-158.
8. Rahman A, Korzekwa KR, Grogan J, Gonzalez FJ, Harris JW. Selective biotransformation of taxol to 6α-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 1994; 54: 5543-5546.
9. Minisalco A, Lundahl J, Regardh CG, Edgar B, Eriksson UG. Inhibition of dihydropyridine metabolism in rat and human liver microsomes by flavonoids found in grapefruit juice. J Pharmacol Exp Ther 1992; 261: 1195-1199.
10. Prueksaritanont T, Tang C, Qiu Y, Mu L, Subramanain R, Lin JH. Effects of fibrates on metabolism of statins in human hepatocytes. Drug Metab Dispos 2002; 30: 1280-1287.
11. Geisel J, Kivistö KT, Griese E-U, Eichelbaum M. The effects of simvastatin is not influenced by CYP2D6 polymorphism. Clin Pharmacol Ther 2002; 71: 595-596.
12. Mück W. Clinical pharmacokinetics of cerivastatin. Clin Pharmacokinet 2000; 39: 99-116.