Effects of fibrates on metabolism of statins in human hepatocytes

Drug Metabolism and Disposition

Volumn 30, Issue 11, 2002, Pages 1280-1287

  Prueksaritanont, Thomayant ^a   Tang, Cuyue ^a   Qiu, Yue ^a   Mu, Lillian ^a   Subramanian, Raju ^a   Lin, Jiunn H ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ATORVASTATIN; CERIVASTATIN; CYTOCHROME P450 2C8; CYTOCHROME P450 3A2; CYTOCHROME P450 3A4; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; GLUCURONOSYLTRANSFERASE; ROSUVASTATIN; SIMVASTATIN; STATIN; ANTILIPEMIC AGENT; CYP2C8 PROTEIN, HUMAN; FLUOROBENZENE; HEPTANOIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; PYRIMIDINE DERIVATIVE; PYRROLE DERIVATIVE; SULFONAMIDE; UNSPECIFIC MONOOXYGENASE;

ARTICLE; COMPETITIVE INHIBITION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG EFFECT; DRUG GLUCURONIDATION; DRUG MECHANISM; DRUG METABOLISM; DRUG OXIDATION; ENZYME INHIBITION; HUMAN; HUMAN CELL; HUMAN TISSUE; IC 50; LIVER CELL; OXIDATION; PRIORITY JOURNAL; ENZYMOLOGY; IN VITRO STUDY; LIVER MICROSOME; METABOLISM; OXIDATION REDUCTION REACTION;

ANTILIPEMIC AGENTS; ARYL HYDROCARBON HYDROXYLASES; FLUOROBENZENES; GEMFIBROZIL; GLUCURONOSYLTRANSFERASE; HEPATOCYTES; HEPTANOIC ACIDS; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; MICROSOMES, LIVER; OXIDATION-REDUCTION; PROCETOFEN; PYRIMIDINES; PYRROLES; SIMVASTATIN; SULFONAMIDES;

EID: 0036843479     PISSN: 00909556     EISSN: None     Source Type: Journal    
DOI: 10.1124/dmd.30.11.1280     Document Type: Article

References (28)

1. Backman JT, Kyrklund C, Kivistö KT, Wang J-S, and Neuvonen PJ (2000) Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther 68:122-129.
2. Boberg M, Angerbauer R, Fey P, Kanhai WK, Karl W, Kern A, Ploschke J, and Radtke M (1997) Metabolism of cerivastatin by human liver microsomes in vitro: Characterization of primary metabolic pathways and cytochrome P450 isozymes involved. Drug Metab Dispos 25:321-331.
3. Boberg M, Angerbauer R, Kanhai WK, Karl W, Kern A, Radtke M, and Steinke W (1998) Biotransformation of cerivastatin in mice, rats and dogs in vivo. Drug Metab Dispos 26:640-652.
4. Brown CDA, Windass A, Bleasby K, and Lauffart B (2001) Rosuvastatin is a high affinity substrate of hepatic organic anion transporter OATP-C. Atherosclerosis 2 (Suppl 2):90.
5. Cheng H, Schwartz MS, Vickers S, Gilbert JD, Amin RD, Depuy B, Liu L, Rogers JD, Pond SD, Duncan CA, et al. (1994) Metabolic disposition of simvastatin in patients with T-tube drainage. Drug Metab Dispos 22:139-142.
6. Farmer JA (2001) Learning from the cerivastatin experience. Lancet 358:1383-1385.
7. Jacobson W, Kuhn B, Soldner A, Kirchner G, Sewing K-F, Kollman PA, Benet LZ, and Christians U (2000) Lactonization is the critical first step in the disposition of the 3-hydroxy-3-methylglutaryl-CoA reductase inhibitor atorvastatin. Drug Metab Dispos 28:1369-1378.
8. Kyrklund C, Backman JT, Kivistö KT, Neuvonen M, Laitila J, and Neuvonen PJ (2001) Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not by bezafibrate. Clin Pharmacol Ther 69:340-345.
9. 14C]-atorvastatin in patients with T-tube drainage. Proc Aus Soc Clin Exp Pharmacol Toxicol 3:153.
10. McTaggart F, Buckett L, Davidson R, Holdgate G, McCormick A, Schneck D, Smith G, and Warwick M (2001) Preclinical and clinical pharmacology of rosuvastatin, a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor. Am J Cardiol 87 (Suppl):28B-32B.
11. Miller DB and Spence JD (1998) Clinical pharmacokinetics of fibric acid derivatives (fibrates). Clin Pharmacokinet 34:155-162.
12. Mück W (2000) Clinical pharmacokinetics of cerivastatin. Clin Pharmacokinet 39:99-116.
13. Murdock DK, Murdock AK, Murdock RW, Olsen KJ, Frane AM, Kersten ME, Joyce DM, and Gantner SE (1999) Long-term safety and efficacy of combination gemfibrozil and HMG-CoA reductase inhibitors for the treatment of mixed lipid disorders. Am Heart J 138:151-155.
14. Newton DJ, Wang RW, and Lu AHY (1995) Cytochrome P450 inhibitors: Evaluation of specificities in the in vitro metabolism of therapeutic agents by human liver microsomes. Drug Metab Dispos 23:154-158.
15. Prueksaritanont T, Gorham LM, Ma B, Liu L, Yu X, Zhao JJ, Slaughter DE, Arison BH, and Vyas KP (1997) In vitro metabolism of simvastatin in humans: Identification of metabolizing enzymes and effect of the drug on hepatic P450s. Drug Metab Dispos 25:1191-1199.
16. Prueksaritanont T, Ma B, Fang X, Subramanian R, Yu J, and Lin JH (2001) β-Oxidation of simvastatin in mouse liver preparations. Drug Metab Dispos 29:1251-1255.
17. Prueksaritanont T, Ma B, Tang C, Meng Y, Assang C, Lu P, Reider PJ, Lin JH, and Baillie TA (1999) Metabolic interactions between mibefradil and HMG-CoA reductase inhibitors: An in vitro investigation with human liver preparations. Br J Clin Pharmacol 47:291-298.
18. Prueksaritanont T, Subramanian R, Fang X, Ma B, Qiu Y, Lin JH, Pearson PG, and Baillie TA (2002a) Glucuronidation of statins in animals and humans: A novel mechanism of statin lactonization. Drug Metab Dispos 30:505-512.
19. Prueksaritanont T, Zhao J, Ma B, Roadcap B, Tang C, Qiu Y, Liu L, Lin JH, Pearson PG, and Baillie TA (2002b) Mechanistic studies on the metabolic interactions between gemfibrozil and statins. J Pharmacol Exp Ther 301:1042-1051.
20. Rahman A, Korzekwa K, Grogan R, Gonzalez FJ, and Harris JW (1994) Selective biotransformation of taxol to 6α-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54:5543-5546.
21. Rašlová K, Dubovská D, Mongiellová V, and Trnovec T (1997) Relationship between plasma fenofibric acid levels and the effect of micronized fenofibrate on cholesterol, low-densitylipoprotein cholesterol and apolipoprotein B in patients with primary hypercholesterolemia. Eur J Clin Pharmacol 52:101-106.
22. Sabordo L and Sallustio BC (1997) Effects of gemfibrozil and clofibric acid on the uptake of taurocholate by isolated rat hepatocytes. Biochem Pharmacol 54:215-218.
23. Schulz H (1987) Inhibitors of fatty acid oxidation. Life Sci 40:1443-1449.
24. Shek A and Ferrill MJ (2001) Statin-fibrate combination therapy. Ann Pharmacother 35:908-917.
25. Shepherd J (1994) The fibrates in clinical practice: Focus on micronised fenofibrate. Atherosclerosis 110 (Suppl):S55-S63.
26. Soars MG, Burchell B, and Riley RJ (2002) In vitro analysis of human drug glucuronidation and prediction of in vivo metabolic clearance. J Pharmacol Exp Ther 301:382-390.
27. Wen X, Wang J-S, Backman JT, Kivistö KT, and Neuvonen PT (2001) Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9. Drug Metab Dispos 29:1359-1361.
28. Yang BB, Siedlik PH, Smithers JA, Sedman AJ, and Stern RH (1996) Atorvastatin pharmacokinetic interactions with other CYP3A4 substrates: Erythromycin and ethinyl estradiol. Pharm Res (NY) 13 (Suppl 9):S437.