Evaluation of CYP2C8 inhibition in vitro: Utility of montelukast as a selective CYP2C8 probe substrate

Drug Metabolism and Disposition

Volumn 39, Issue 9, 2011, Pages 1546-1554

  VandenBrink, Brooke M ^a   Foti, Robert S ^a   Rock, Dan A ^a   Wienkers, Larry C ^a   Wahlstrom, Jan L ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMODIAQUINE; BENZBROMARONE; CELECOXIB; CERIVASTATIN; CLOTRIMAZOLE; CYTOCHROME P450 2C8; ESTRADIOL; FLUINDOSTATIN; GEMFIBROZIL; MEDROXYPROGESTERONE; MEVINOLIN; MONTELUKAST; NIFEDIPINE; PACLITAXEL; PIOGLITAZONE; QUERCETIN; REPAGLINIDE; ROSIGLITAZONE; SERTRALINE; SIMVASTATIN; TAMOXIFEN; TRIAMCINOLONE; TRIMETHOPRIM;

ARTICLE; COMPETITIVE INHIBITION; CONTROLLED STUDY; DRUG METABOLISM; DRUG OXIDATION; DRUG POTENCY; DRUG SENSITIVITY; ENZYME INHIBITION; ENZYME SUBSTRATE; HUMAN; HUMAN CELL; IN VITRO STUDY; IN VIVO STUDY; LIVER MICROSOME; PHENOTYPE; PRIORITY JOURNAL;

ACETATES; AMODIAQUINE; ARYL HYDROCARBON HYDROXYLASES; BINDING SITES; CARBAMATES; DRUG INTERACTIONS; HUMANS; MICROSOMES, LIVER; PACLITAXEL; PIPERIDINES; QUINOLINES; SENSITIVITY AND SPECIFICITY; SUBSTRATE SPECIFICITY; THIAZOLIDINEDIONES;

EID: 80051966185     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.111.039065     Document Type: Article

References (50)

1. Backman J.T., Kyrklund C., Neuvonen M, and Neuvonen P.J. (2002) Gemfibrozil greatly increases plasma concentrations of cerivastatin. Clin Pharmacol Ther 72:685-691. (Pubitemid 36021007)
2. Baer B.R., Wienkers LC, and Rock D.A. (2007) Time- Dependent inactivation of P450 3A4 by raloxifene: identification of Cys239 as the site of apoprotein alkylation. Chem Res Toxicol 20:954-964. (Pubitemid 47035350)
3. Balani S.K., Xu X., Pratha V., Koss M.A., Amin R.D., Dufresne C., Miller R.R., Arison B.H., Doss G.A., Chiba M., et al. (1997) Metabolic profiles of montelukast sodium (Singulair), a potent cysteinyl leukotriene1 receptor antagonist, in human plasma and bile. Drug Metab Dispos 25:1282-1287. (Pubitemid 27490673)
4. Chiba M., Xu X., Nishime J.A., Balani SK, and Lin J.H. (1997) Hepatic microsomal metabolism of montelukast, a potent leukotriene D4 receptor antagonist, in humans. Drug Metab Dispos 25:1022-1031. (Pubitemid 27396488)
5. Davidson M.H. (2002) Controversy surrounding the safety of cerivastatin. Expert Opin Drug Saf 1:207-212.
6. Deng L.J., Wang F, and Li H.D. (2005) Effect of gemfibrozil on the pharmacokinetics of pioglitazone. Eur J Clin Pharmacol 61:831-836. (Pubitemid 41720271)
7. Farmer J.A. (2001) Learning from the cerivastatin experience. Lancet 358:1383-1385.
8. Filppula A.M., Laitila J., Neuvonen PJ, and Backman J.T. (2011) Reevaluation of the microsomal metabolism of montelukast: Major contribution by CYP2C8 at clinically relevant concentrations. Drug Metab Dispos 39:904-911.
9. Foti R.S., Rock D.A., Wienkers LC, and Wahlstrom J.L. (2010) Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation. Drug Metab Dispos 38:981-987.
10. Foti RS and Wahlstrom J.L. (2008) CYP2C19 inhibition: The impact of substrate probe selection on in vitro inhibition profiles. Drug Metab Dispos 36:523-528. (Pubitemid 351397977)
11. Gelboin H.V., Krausz K.W., Goldfarb I., Buters J.T., Yang S.K., Gonzalez F.J., Korzekwa KR, and Shou M. (1995) Inhibitory and non- Inhibitory monoclonal antibodies to human cytochrome P450 3A3/4. Biochem Pharmacol 50:1841-1850. (Pubitemid 26011393)
12. Hatorp V and Thomsen M.S. (2000) Drug interaction studies with repaglinide: Repaglinide on digoxin or theophylline pharmacokinetics and cimetidine on repaglinide pharmacokinetics. J Clin Pharmacol 40:184-192.
13. Hinton L.K., Galetin A, and Houston J.B. (2008) Multiple inhibition mechanisms and prediction of drug- Drug interactions: status of metabolism and transporter models as exemplified by gemfibrozil- Drug interactions: status of metabolism and transporter models as exemplified by gemfibrozilDrug interactions. Pharm Res 25:1063-1074. (Pubitemid 351521103)
14. Hruska M.W., Amico J.A., Langaee T.Y., Ferrell R.E., Fitzgerald SM, and Frye R.F. (2005) The effect of trimethoprim on CYP2C8 mediated rosiglitazone metabolism in human liver microsomes and healthy subjects. Br J Clin Pharmacol 59:70-79. (Pubitemid 40040098)
15. Huang S.M., Temple R., Throckmorton DC, and Lesko L.J. (2007) Drug interaction studies: Study design, data analysis, and implications for dosing and labeling. Clin Pharmacol Ther 81:298-304. (Pubitemid 46174829)
16. Jaakkola T., Backman J.T., Neuvonen M, and Neuvonen P.J. (2005) Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics of pioglitazone. Clin Pharmacol Ther 77:404-414. (Pubitemid 40719268)
17. Jaakkola T., Backman J.T., Neuvonen M., Niemi M, and Neuvonen P.J. (2006) Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone. Eur J Clin Pharmacol 62:503-509.
18. Kajosaari L.I., Niemi M., Backman JT, and Neuvonen P.J. (2006) Telithromycin, but not montelukast, increases the plasma concentrations and effects of the cytochrome P450 3A4 and 2C8 substrate repaglinide. Clin Pharmacol Ther 79:231-242.
19. Karonen T., Filppula A., Laitila J., Niemi M., Neuvonen PJ, and Backman J.T. (2010) Gemfibrozil markedly increases the plasma concentrations of montelukast: A previously unrecognized role for CYP2C8 in the metabolism of montelukast. Clin Pharmacol Ther 88:223-230.
20. Kenworthy K.E., Bloomer J.C., Clarke SE, and Houston J.B. (1999) CYP3A4 drug interactions: Correlation of 10 in vitro probe substrates. Br J Clin Pharmacol 48:716-727. (Pubitemid 29520596)
21. Kim K.A., Park P.W., Kim KR, and Park J.Y. (2007) Effect of multiple doses of montelukast on the pharmacokinetics of rosiglitazone, a CYP2C8 substrate, in humans. Br J Clin Pharmacol 63:339-345.
22. Kivistö K.T., Kantola T, and Neuvonen P.J. (1998) Different effects of itraconazole on the pharmacokinetics of fluvastatin and lovastatin. Br J Clin Pharmacol 46:49-53. (Pubitemid 28308424)
23. Kumar V., Wahlstrom J.L., Rock D.A., Warren C.J., Gorman LA, and Tracy T.S. (2006) CYP2C9 inhibition: Impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab Dispos 34:1966-1975. (Pubitemid 44837757)
24. Lai X.S., Yang L.P., Li X.T., Liu J.P., Zhou ZW, and Zhou S.F. (2009) Human CYP2C8: Structure, substrate specificity, inhibitor selectivity, inducers and polymorphisms. Curr Drug Metab 10:1009-1047.
25. Mayhew B.S., Jones DR, and Hall S.D. (2000) An in vitro model for predicting in vivo inhibition of cytochrome P450 3A4 by metabolic intermediate complex formation. Drug Metab Dispos 28:1031-1037. (Pubitemid 30660356)
26. Mazzu A.L., Lasseter K.C., Shamblen E.C., Agarwal V., Lettieri J, and Sundaresen P. (2000) Itraconazole alters the pharmacokinetics of atorvastatin to a greater extent than either cerivastatin or pravastatin. Clin Pharmacol Ther 68:391-400.
27. Mück W., Ritter W., Dietrich H., Frey R, and Kuhlmann J. (1997) Influence of the antacid Maalox and the H2- Antagonist cimetidine on the pharmacokinetics of cerivastatin. Int J Clin Pharmacol Ther 35:261-264. (Pubitemid 27268176)
28. Niemi M., Backman J.T., Granfors M., Laitila J., Neuvonen M, and Neuvonen P.J. (2003a) Gemfibrozil considerably increases the plasma concentrations of rosiglitazone. Diabetologia 46:1319-1323. (Pubitemid 37297200)
29. Niemi M., Backman J.T., Neuvonen M, and Neuvonen P.J. (2003b) Effects of gemfibrozil, itraconazole, and their combination on the pharmacokinetics and pharmacodynamics of repaglinide: Potentially hazardous interaction between gemfibrozil and repaglinide. Diabetologia 46:347-351. (Pubitemid 36547589)
30. Niemi M., Backman JT, and Neuvonen P.J. (2004a) Effects of trimethoprim and rifampin on the pharmacokinetics of the cytochrome P450 2C8 substrate rosiglitazone. Clin Pharmacol Ther 76:239-249.
31. Niemi M., Kajosaari L.I., Neuvonen M., Backman JT, and Neuvonen P.J. (2004b) The CYP2C8 inhibitor trimethoprim increases the plasma concentrations of repaglinide in healthy subjects. Br J Clin Pharmacol 57:441-447. (Pubitemid 38519649)
32. Ogilvie B.W., Zhang D., Li W., Rodrigues A.D., Gipson A.E., Holsapple J., Toren P, and Parkinson A. (2006) Glucuronidation converts gemfibrozil to a potent, metabolism- Dependent inhibitor of CYP2C8: implications for drug- Dependent inhibitor of CYP2C8: implications for drugDrug interactions. Drug Metab Dispos 34:191-197. (Pubitemid 43042661)
33. Po AL and Zhang W.Y. (1998) What lessons can be learnt from withdrawal of mibefradil from the market? Lancet 351:1829-1830.
34. Ragueneau-Majlessi I., Boulenc X., Rauch C., Hachad H, and Levy R.H. (2007) Quantitative correlations among CYP3A sensitive substrates and inhibitors: Literature analysis. Curr Drug Metab 8:810-814. (Pubitemid 350238910)
35. Rahman A., Korzekwa K.R., Grogan J., Gonzalez FJ, and Harris J.W. (1994) Selective biotransformation of Taxol to 6 α-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 54:5543-5546.
36. Regal K.A., Kunze K.L., Peter RM, and Nelson S.D. (2005) Oxidation of caffeine by CYP1A2: Isotope effects and metabolic switching. Drug Metab Dispos 33:1837-1844. (Pubitemid 41697269)
37. Rock D.A., Foti RS, and Pearson J.T. (2008) The combination of chemical and antibody inhibitors for superior P450 3A inhibition in reaction phenotyping studies. Drug Metab Dispos 36:2410-2413.
38. Rostami-Hodjegan A and Tucker G.T. (2007) Simulation and prediction of in vivo drug metabolism in human populations from in vitro data. Nat Rev Drug Discov 6:140-148. (Pubitemid 46745341)
39. Roustit M., Blondel E., Villier C., Fonrose X, and Mallaret M.P. (2010) Symptomatic hypoglycemia associated with trimethoprim/sulfamethoxazole and repaglinide in a diabetic patient. Ann Pharmacother 44:764-767.
40. Schoch G.A., Yano J.K., Sansen S., Dansette P.M., Stout CD, and Johnson E.F. (2008) Determinants of cytochrome P450 2C8 substrate binding: structures of complexes with montelukast, troglitazone, felodipine, and 9-cis-retinoic acid. J Biol Chem 283:17227-17237.
41. Schoch G.A., Yano J.K., Wester M.R., Griffin K.J., Stout CD, and Johnson E.F. (2004) Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J Biol Chem 279:9497-9503. (Pubitemid 38296017)
42. Shitara Y., Hirano M., Sato H, and Sugiyama Y. (2004) Gemfibrozil and its glucuronide inhibit the organic anion transporting polypeptide 2 (OATP2/OATP1B1:SLC21A6)- Mediated hepatic uptake and CYP2C8- Mediated hepatic uptake and CYP2C8Mediated metabolism of cerivastatin: analysis of the mechanism of the clinically relevant drug- Mediated hepatic uptake and CYP2C8Mediated metabolism of cerivastatin: analysis of the mechanism of the clinically relevant drugDrug interaction between cerivastatin and gemfibrozil. J Pharmacol Exp Ther 311:228-236. (Pubitemid 39287802)
43. Spence J.D., Munoz C.E., Hendricks L., Latchinian L, and Khouri H.E. (1995) Pharmacokinetics of the combination of fluvastatin and gemfibrozil. Am J Cardiol 76:80A-83A.
44. Stresser D.M., Blanchard A.P., Turner S.D., Erve J.C., Dandeneau A.A., Miller VP, and Crespi C.L. (2000) Substrate-dependent modulation of CYP3A4 catalytic Activity: analysis of 27 test compounds with four fluorometric substrates. Drug Metab Dispos 28:1440-1448.
45. Tornio A., Niemi M., Neuvonen PJ, and Backman J.T. (2008a) Trimethoprim and the CYP2C8*3 allele have opposite effects on the pharmacokinetics of pioglitazone. Drug Metab Dispos 36:73-80.
46. Tornio A., Niemi M., Neuvonen M., Laitila J., Kalliokoski A., Neuvonen PJ, and Backman J.T. (2008b) 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 84:403-411.
47. Wahlstrom J.L., Rock D.A., Slatter GS, and Wienkers L.C. (2006) Advances in predicting CYP-mediated drug interactions in the drug discovery setting. Expert Opin Drug Discov 1:677-691.
48. Walsky R.L., Gaman EA, and Obach R.S. (2005) Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol 45:68-78.
49. Walsky RL and Obach R.S. (2004) Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647-660. (Pubitemid 38668158)
50. Wienkers LC and Heath T.G. (2005) Predicting in vivo drug interactions from in vitro drug discovery data. Nat Rev Drug Discov 4:825-833. (Pubitemid 41553963)