The CYP2C8 inhibitor gemfibrozil does not affect the pharmacokinetics of zafirlukast

European Journal of Clinical Pharmacology

Volumn 67, Issue 2, 2011, Pages 151-155

  Karonen, Tiina ^a   Neuvonen, Pertti J ^a   Backman, Janne T ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

CYP2C8; Drug interaction; Gemfibrozil; Pharmacokinetics; Zafirlukast

Indexed keywords

CYTOCHROME P450 2C8; GEMFIBROZIL; PLACEBO; ZAFIRLUKAST;

ADULT; ARTICLE; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG ELIMINATION; DRUG HALF LIFE; DRUG METABOLISM; ENZYME ACTIVITY; EVENING DOSAGE; FEMALE; HUMAN; HUMAN EXPERIMENT; IN VIVO STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MORNING DOSAGE; NORMAL HUMAN; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SINGLE DRUG DOSE; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADULT; ARYL HYDROCARBON HYDROXYLASES; CROSS-OVER STUDIES; DRUG INTERACTIONS; FEMALE; GEMFIBROZIL; GLUCURONATES; HUMANS; MALE; TOSYL COMPOUNDS; YOUNG ADULT;

EID: 79151474510     PISSN: 00316970     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00228-010-0908-0     Document Type: Article

References (27)

1. WJ Calhoun 1998 Summary of clinical trials with zafirlukast Am J Respir Crit Care Med 157 6 Pt 1 S238 S246 1:STN:280:DyaK1czgvFyhsw%3D%3D
2. JS Kelloway 1997 Zafirlukast: the first leukotriene-receptor antagonist approved for the treatment of asthma Ann Pharmacother 31 9 1012 1021 1:CAS:528:DyaK2sXmtFGrt7o%3D 9296243
3. BJ Lipworth 1999 Leukotriene-receptor antagonists Lancet 353 9146 57 62 1:CAS:528:DyaK1MXmtVarug%3D%3D 10.1016/S0140-6736(98)09019-9 10023966
4. T Karonen A Filppula J Laitila M Niemi PJ Neuvonen JT Backman 2010 Gemfibrozil markedly increases the plasma concentrations of montelukast: a previously unrecognized role for CYP2C8 in the metabolism of montelukast Clin Pharmacol Ther 88 2 223 230 1:CAS:528:DC%2BC3cXptVCksL4%3D 10.1038/clpt.2010.73 20592724
5. AstraZeneca (1999) Accolate pharmacology review. http://www.accessdata. fda.gov/drugsatfda-docs/nda/99/20-547-S007-ACCOLATE-PHARMR.PDF. Accessed June 2010
6. PN Dekhuijzen PP Koopmans 2002 Pharmacokinetic profile of zafirlukast Clin Pharmacokinet 41 2 105 114 10.2165/00003088-200241020-00003 11888331
7. AstraZeneca LP (2009) Accolate label. http://www.accessdata.fda.gov/ drugsatfda-docs/label/2009/020547s027lbl.pdf. Accessed May 2010
8. RD Savidge KH Bui BK Birmingham JL Morse RC Spreen 1998 Metabolism and excretion of zafirlukast in dogs, rats, and mice Drug Metab Dispos 26 11 1069 1076 1:CAS:528:DyaK1cXnt1Gru74%3D 9806948
9. K Kassahun K Skordos I McIntosh D Slaughter GA Doss TA Baillie GS Yost 2005 Zafirlukast metabolism by cytochrome P450 3A4 produces an electrophilic alpha, beta-unsaturated iminium species that results in the selective mechanism-based inactivation of the enzyme Chem Res Toxicol 18 9 1427 1437 1:CAS:528:DC%2BD2MXnslOrsbk%3D 10.1021/tx050092b 16167835
10. RL Walsky EA Gaman RS Obach 2005 Examination of 209 drugs for inhibition of cytochrome P450 2C8 J Clin Pharmacol 45 1 68 78 1:CAS:528: DC%2BD2MXks1Sls7k%3D 10.1177/0091270004270642 15601807
11. RI Shader BW Granda LL von Moltke GM Giancarlo DJ Greenblatt 1999 Inhibition of human cytochrome P450 isoforms in vitro by zafirlukast Biopharm Drug Dispos 20 8 385 388 1:CAS:528:DC%2BD3cXlt1Wht70%3D 10.1002/1099- 081X(199911)20:8<385:AID-BDD203>3.0.CO;2-7 10870095
12. T Jaakkola J Laitila PJ Neuvonen JT Backman 2006 Pioglitazone is metabolised by CYP2C8 and CYP3A4 in vitro: potential for interactions with CYP2C8 inhibitors Basic Clin Pharmacol Toxicol 99 1 44 51 1:CAS:528: DC%2BD28XnvF2msLs%3D 10.1111/j.1742-7843.2006.pto-437.x 16867170
13. RL Walsky RS Obach EA Gaman JP Gleeson WR Proctor 2005 Selective inhibition of human cytochrome P4502C8 by montelukast Drug Metab Dispos 33 3 413 418 1:CAS:528:DC%2BD2MXisFSgtro%3D 10.1124/dmd.104.002766 15608135
14. T Jaakkola JT Backman M Neuvonen M Niemi PJ Neuvonen 2006 Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone Eur J Clin Pharmacol 62 7 503 509 1:CAS:528:DC%2BD28XmsFOntLY%3D 10.1007/s00228-006-0136-9 16670899
15. Y Shitara M Hirano H Sato Y Sugiyama 2004 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 311 1 228 236 1:CAS:528:DC%2BD2cXosVKrt7g%3D 10.1124/jpet.104.068536 15194707
16. BW Ogilvie D Zhang W Li AD Rodrigues AE Gipson J Holsapple P Toren A Parkinson 2006 Glucuronidation converts gemfibrozil to a potent, metabolism-dependent inhibitor of CYP2C8: implications for drug-drug interactions Drug Metab Dispos 34 1 191 197 1:CAS:528:DC%2BD28XhslyitQ%3D%3D 10.1124/dmd.105.007633 16299161
17. BR Baer RK Delisle A Allen 2009 Benzylic oxidation of gemfibrozil-1-O-beta-glucuronide by P450 2C8 leads to heme alkylation and irreversible inhibition Chem Res Toxicol 22 7 1298 1309 1:CAS:528: DC%2BD1MXmtVGlsLw%3D 10.1021/tx900105n 19445523
18. A Tornio M Niemi M Neuvonen J Laitila A Kalliokoski PJ Neuvonen JT Backman 2008 The effect of gemfibrozil on repaglinide pharmacokinetics persists for at least 12 h after the dose: evidence for mechanism-based inhibition of CYP2C8 in vivo Clin Pharmacol Ther 84 3 403 411 1:CAS:528:DC%2BD1cXhtVShtr7K 10.1038/clpt.2008.34 18388877
19. JT Backman J Honkalammi M Neuvonen KJ Kurkinen A Tornio M Niemi PJ Neuvonen 2009 CYP2C8 activity recovers within 96 hours after gemfibrozil dosing: estimation of CYP2C8 half-life using repaglinide as an in vivo probe Drug Metab Dispos 37 12 2359 2366 1:CAS:528:DC%2BD1MXhsFajtr7P 10.1124/dmd.109.029728 19773535
20. JT Backman C Kyrklund M Neuvonen PJ Neuvonen 2002 Gemfibrozil greatly increases plasma concentrations of cerivastatin Clin Pharmacol Ther 72 6 685 691 1:CAS:528:DC%2BD3sXlt1SjsQ%3D%3D 10.1067/mcp.2002.128469 12496749
21. T Jaakkola JT Backman M Neuvonen PJ Neuvonen 2005 Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone Clin Pharmacol Ther 77 5 404 414 1:CAS:528:DC%2BD2MXktFCrtLg%3D 10.1016/j.clpt.2004.12.266 15900286
22. M Niemi JT Backman M Neuvonen PJ Neuvonen 2003 Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: potentially hazardous interaction between gemfibrozil and repaglinide Diabetologia 46 3 347 351 1:CAS:528:DC%2BD3sXksVWjtL0%3D 12687332
23. LJ Deng F Wang HD Li 2005 Effect of gemfibrozil on the pharmacokinetics of pioglitazone Eur J Clin Pharmacol 61 11 831 836 1:CAS:528: DC%2BD2MXht1Gqu7%2FF 10.1007/s00228-005-0042-6 16283275
24. X Wen JS Wang JT Backman KT Kivistö PJ Neuvonen 2001 Gemfibrozil is a potent inhibitor of human cytochrome P450 2C9 Drug Metab Dispos 29 11 1359 1361 1:CAS:528:DC%2BD3MXnsl2ku7k%3D 11602509
25. JS Wang M Neuvonen X Wen JT Backman PJ Neuvonen 2002 Gemfibrozil inhibits CYP2C8-mediated cerivastatin metabolism in human liver microsomes Drug Metab Dispos 30 12 1352 1356 10.1124/dmd.30.12.1352 12433802
26. JJ Lilja JT Backman PJ Neuvonen 2005 Effect of gemfibrozil on the pharmacokinetics and pharmacodynamics of racemic warfarin in healthy subjects Br J Clin Pharmacol 59 4 433 439 1:CAS:528:DC%2BD2MXktFals7o%3D 10.1111/j.1365-2125.2004.02323.x 15801938
27. DV Bharathi A Naidu B Jagadeesh KN Laxmi PR Laxmi PR Reddy R Mullangi 2008 Development and validation of a sensitive LC-MS/MS method with electrospray ionization for quantitation of zafirlukast, a selective leukotriene antagonist in human plasma: application to a clinical pharmacokinetic study Biomed Chromatogr 22 6 645 653 1:CAS:528:DC%2BD1cXnslWksrg%3D 10.1002/bmc.983 18254142