The effects of multiple doses of fenofibrate on the pharmacokinetics of pravastatin and its 3α-hydroxy isomeric metabolite

Journal of Clinical Pharmacology

Volumn 45, Issue 8, 2005, Pages 947-953

  Gustavson, Linda E ^a   Schweitzer, Sarah M ^a   Koehne Voss, Stephan ^b   Achari, Ramanuj ^a   Chira, Titus O ^a   Esslinger, Hans Ulrich ^b   Yannicelli, H Daniel ^a  

^a ABBOTT LABORATORIES   (United States)

^b ABBOTT GMBH AND CO KG   (Germany)

Author keywords

3 hydroxy iso pravastatin; Drug interactions; Fenofibrate; Pharmacokinetics; Pravastatin

Indexed keywords

3ALPHA HYDROXYPRAVASTATIN; DRUG METABOLITE; FENOFIBRATE; FIBRIC ACID DERIVATIVE; GEMFIBROZIL; PRAVASTATIN; UNCLASSIFIED DRUG;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLOOD SAMPLING; CLINICAL TRIAL; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG ELIMINATION; DRUG EXPOSURE; DRUG HALF LIFE; DRUG SAFETY; ELECTROCARDIOGRAM; FEMALE; HEADACHE; HUMAN; HUMAN EXPERIMENT; ISOMER; LABORATORY TEST; MALE; MULTIPLE DRUG DOSE; NORMAL HUMAN; PHASE 1 CLINICAL TRIAL; PHYSICAL EXAMINATION;

ADULT; ANTICHOLESTEREMIC AGENTS; ANTILIPEMIC AGENTS; AREA UNDER CURVE; DRUG INTERACTIONS; FEMALE; HALF-LIFE; HUMANS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; ISOMERISM; MALE; METABOLIC CLEARANCE RATE; MIDDLE AGED; PRAVASTATIN; PROCETOFEN;

EID: 23044464472     PISSN: 00912700     EISSN: None     Source Type: Journal    
DOI: 10.1177/0091270005278085     Document Type: Article

References (24)

1. TriCor tablets [US prescribing information]. Abbott Park, Ill: Abbott Laboratories; 2003.
2. Keating GM, Ormrod D. Micronized fenofibrate, an updated review of its clinical efficacy in tho management of clyslipidaemia. Drugs. 2002;62:1909-1944.
3. Pravachol tablets [US prescribing information]. Princeton, NJ: Bristol-Myers Squibb; 2002.
4. Grundy SM, Cleeman JI, Merz NB, et al, for the Coordinating Committee of the National Cholesterol Education Program. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III guidelines. Circulation. 2004;110: 227-239.
5. Pan W-J, Gustavson LE, Achari R, et al. Lack of a clinically significant pharmacokinetic interaction between fenofibrate and pravastatin in healthy volunteers. J Clin Pharmacol. 2000;40:316-323.
6. Ellen RLB, McPherson R. Long-term efficacy and safety of fenofibrate and a statin in the treatment of combined hyperlipidemia. Am J Cardiol. 1998;81:60B-65B.
7. Kyrklund C, Backman JT, Neuvonen M, Neuvonen PJ. Gemfibrozil increases plasma pravastatin concentrations and reduces pravastatin renal clearance. Clin Pharmacol Ther. 2003;73:538-544.
8. Backman JT, Kyrklund C, Kivisto KT, Wang J-S, Neuvonen PJ. Plasma concentrations of active simvastatin acid are increased by gemfibrozil. Clin Pharmacol Ther. 2000;68:122-129.
9. Kyrklund C, Backman JT, Kivisto KT, Neuvonen M, Laitila J, Neuvonen PJ. Plasma concentrations of active lovastatin acid are markedly increased by gemfibrozil but not bezafibrate. Clin Pharmacol Ther. 2001;69:340-345.
10. Backman JT, Kyrklund C, Neuvonen M, Neuvonen PJ. Gemfibrozil greatly increases plasma concentrations of cerivastatin. Clin Pharmacol Ther. 2002;72:685-691.
11. Department of Health and Human Services, Food and Drug Administration. Coding Symbols for Thesaurus of Adverse Reaction Terms. 5th ed. Rockville, Md: Department of Health and Human Services, Food and Drug Administration: 1995.
12. Singhvi SM, Pan HY, Morrison RA, Willard DA. Disposition of pravastatin sodium, a tissue-selective HMG-CoA reductase inhibitor, in healthy subjects. Br J Clin Pharmacol. 1990;29:239-243.
13. Lopid tablets [US prescribing information]. New York: Pfizer; 2003.
14. Shitara Y, Hirano M, Sato H, Sugiyama Y. Gemfibrozil and its glucuronide inhibit the organic anion transporting polypeptide 2 (OATP2/OATP1B1:SLC21 A6)-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;31:228-236.
15. Hsiang B, Zhu Y, Wang Z, et al. A novel human organic anion transporting polypeptide (OATP2): identification of a liver-specific human organic anion transporting polypeptide and identification of rat and human hydroxymethylglutaryl-CoA reductase inhibitor transporters. J Biol Chem. 1999;274:37161-37168.
16. Spence JD, Munoz CE, Hendricks L, Latchinian L, Khouri HE. Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol. 1995;76:80A-83A.
17. 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;73:554-565.
18. Mwinyi J, Johne A, Bauer S, Roots I, Gerloff T. Evidence for inverse effects of OATP-C (SLC21A6) *5 and *1b haplotypes on pravastatin kinetics. Clin Pharmacol Ther. 2004;75:415-421.
19. 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;14:429-440.
20. Hatanaka T. Clinical pharmacokinetics of pravastatin. Clin Pharmacokinet. 2000;39:397-412.
21. Kitazawa E, Tamura N, Iwabuchi H, et al. Biotransformation of pravastatin sodium (I) mechanisms of enzymic transformation and epimerization of an allylic hydroxy group of pravastatin sodium. Biochem Biophys Res Comm. 1993;192:597-602.
22. Jacobsen W, Kirchner G, Hallensieben K, et al. Comparison of cytochrome P-450-dependciit metabolism and drug interactions of the 3-hydroxy-3- methylglutaryl-CoA reductase inhibitors lovastatin and pravastatin in the liver. Drug Metab Dispos. 1999;27:173-179.
23. Bertz R, Hsu A, Lam W, et al. Pharmacokinetic interactions between lopinavir/ritonavir (ABT-378/r) and other non-HIV drugs. AIDS. 2000;14:S100.
24. Wang E-J, Casciano CN, Clement RP, Johnson WW. HMG-CoA reductase inhibitors (statins) characterized as direct inhibitors' of P-glycoprotein. Pharm Res. 2001;18:800-806.