Evaluation of six proton pump inhibitors as inhibitors of various human cytochromes P450: Focus on cytochrome P450 2C19

Drug Metabolism and Disposition

Volumn 40, Issue 9, 2012, Pages 1698-1711

  Zvyaga, Tatyana ^a   Chang, Shu Ying ^a   Chen, Cliff ^a   Yang, Zheng ^a   Vuppugalla, Ragini ^a   Hurley, Jeremy ^a   Thorndike, Denise ^a   Wagner, Andrew ^a   Chimalakonda, Anjaneya ^a   Rodrigues, A David ^a  

^a BRISTOL MYERS SQUIBB   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 1A2; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C8; CYTOCHROME P450 2C9; CYTOCHROME P450 2D6; CYTOCHROME P450 3A4; CYTOCHROME P450 INHIBITOR; DIAZEPAM; DIAZEPAM N DEMETHYLASE; ESOMEPRAZOLE; LANSOPRAZOLE; N DEMETHYLASE; OMEPRAZOLE; PANTOPRAZOLE; PROTON PUMP INHIBITOR; RABEPRAZOLE; RECOMBINANT ENZYME; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG METABOLISM; DRUG POTENCY; DRUG PROTEIN BINDING; DRUG SCREENING; ENZYME ACTIVITY; ENZYME INHIBITION; HUMAN; HUMAN CELL; IC 50; IN VIVO STUDY; LIVER CELL; LIVER MICROSOME; PRIORITY JOURNAL; SINGLE DRUG DOSE;

2-PYRIDINYLMETHYLSULFINYLBENZIMIDAZOLES; ARYL HYDROCARBON HYDROXYLASES; BIOTRANSFORMATION; CELLS, CULTURED; COMPUTER SIMULATION; DEALKYLATION; DIAZEPAM; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG INTERACTIONS; ENZYME INHIBITORS; ESOMEPRAZOLE SODIUM; HEPATOCYTES; HUMANS; KINETICS; LIVER; MICROSOMES, LIVER; MODELS, BIOLOGICAL; NADP; OMEPRAZOLE; PROTON PUMP INHIBITORS; RECOMBINANT PROTEINS; SUBSTRATE SPECIFICITY;

EID: 84865180550     PISSN: 00909556     EISSN: 1521009X     Source Type: Journal    
DOI: 10.1124/dmd.112.045575     Document Type: Article

References (51)

1. Abelö A, Andersson TB, Antonsson M, Naudot AK, Skånberg I, and Weidolf L (2000) Stereoselective metabolism of omeprazole by human cytochrome P450 enzymes. Drug Metab Dispos 28:966-972. (Pubitemid 30612617)
2. Andersson T, Cederberg C, Edvardsson G, Heggelund A, and Lundborg P (1990) Effect of omeprazole treatment on diazepam plasma levels in slow versus normal rapid metabolizers of omeprazole. Clin Pharmacol Ther 47:79-85. (Pubitemid 20041214)
3. Andersson T, Hassan-Alin M, Hasselgren G, Röhss K, and Weidolf L (2001) Pharmacokinetic studies with esomeprazole, the (S)-isomer of omeprazole. Clin Pharmacokinet 40:411-426. (Pubitemid 32656078)
4. Angiolillo DJ, Gibson CM, Cheng S, Ollier C, Nicolas O, Bergougnan L, Perrin L, LaCreta FP, Hurbin F, and Dubar M (2011) Differential effects of omeprazole and pantoprazole on the pharmacodynamics and pharmacokinetics of clopidogrel in healthy subjects: randomized, placebo-controlled, crossover comparison studies. Clin Pharmacol Ther 89:65-74.
5. Baldwin RM, Ohlsson S, Pedersen RS, Mwinyi J, Ingelman-Sundberg M, Eliasson E, and Bertilsson L (2008) Increased omeprazole metabolism in carriers of the CYP2C19*17 allele; a pharmacokinetic study in healthy volunteers. Br J Clin Pharmacol 65:767-774. (Pubitemid 351535091)
6. Blume H, Donath F, Warnke A, and Schug BS (2006) Pharmacokinetic drug interaction profiles of proton pump inhibitors. Drug Safety 29:769-784. (Pubitemid 44352242)
7. Boulenc X, Djebli N, Shi J, Perrin L, Brian W, Van Horn R, and Hurbin F (2012) Effects of omeprazole and genetic polymorphism of CYP2C19 on the clopidogrel active metabolite. Drug Metab Dispos 40:187-197.
8. Frelinger AL, Lee RD, Mulford DJ, Wu J, Nudurupati S, Nigam A, Brooks JK, Bhatt DL, and Michelson AD (2012) A randomized, 2-period, crossover design study to assess the effects of dexlansoprazole, lansoprazole, esomeprazole, and omeprazole on the steady-state pharmacokinetics and pharmacodynamics of clopidogrel in healthy volunteers. J Am Coll Cardiol 59:1304-1311.
9. Furuta T, Iwaki T, and Umemura K (2010) Influences of different proton pump inhibitors on the anti-platelet function of clopidogrel in relation to CYP2C19 genotypes. Br J Clin Pharmacol 70:383-392.
10. Gerloff J, Mignot A, Barth H, and Heintze K (1996) Pharmacokinetics and absolute bioavailability of lansoprazole. Eur J Clin Pharmacol 50:293-297. (Pubitemid 26188280)
11. Gugler R, Hartmann M, Rudi J, Brod I, Huber R, Steinijans VW, Bliesath H, Wurst W, and Klotz U (1996) Lack of pharmacokinetic interaction of pantoprazole with diazepam in man. Br J Clin Pharmacol 42:249-252. (Pubitemid 26255076)
12. Hagihara K, Kazui M, Kurihara A, Yoshiike M, Honda K, Okazaki O, Farid NA, and Ikeda T (2009) A possible mechanism for the differences in efficiency and variability of active metabolite formation from thienopyridine antiplatelet agents, prasugrel and clopidogrel. Drug Metab Dispos 37:2145-2152.
13. Hunfeld NG, Mathot RA, Touw DJ, van Schaik RH, Mulder PG, Franck PF, Kuipers EJ, and Geus WP (2008) Effect of CYP2C19*2 and*17 mutations on pharmacodynamics and kinetics of proton pump inhibitors in Caucasians. Br J Clin Pharmacol 65:752-760. (Pubitemid 351535088)
14. Ishizaki T, Chiba K, Manabe K, Koyama E, Hayashi M, Yasuda S, Horai Y, Tomono Y, Yamato C, and Toyoki T (1995) Comparison of the interaction potential of a new proton pump inhibitor, E3810, versus omeprazole with diazepam in extensive and poor metabolizers of S-mephenytoin 4′-hydroxylation. Clin Pharmacol Ther 58:155-164.
15. Ito K, Hallifax D, Obach RS, and Houston JB (2005) Impact of parallel pathways of drug elimination and multiple cytochrome P450 involvement on drug-drug interactions: CYP2D6 paradigm. Drug Metab Dispos 33:837-844. (Pubitemid 40686638)
16. Jones HM, Hallifax D, and Houston JB (2004) Quantitative prediction of the in vivo inhibition of diazepam metabolism by omeprazole using rat liver microsomes and hepatocytes. Drug Metab Dispos 32:572-580. (Pubitemid 38535037)
17. Karam WG, Goldstein JA, Lasker JM, and Ghanayem BI (1996) Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. Drug Metab Dispos 24:1081-1087. (Pubitemid 26346220)
18. Kazui M, Nishiya Y, Ishizuka T, Hagihara K, Farid NA, Okazaki O, Ikeda T, and Kurihara A (2010) Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite. Drug Metab Dispos 38:92-99.
19. Klotz U, Avant GR, Hoyumpa A, Schenker S, and Wilkinson GR (1975) The effects of age and liver disease on the disposition and elimination of diazepam in adult man. J Clin Invest 55:347-359.
20. Ko JW, Sukhova N, Thacker D, Chen P, and Flockhart DA (1997) Evaluation of omeprazole and lansoprazole as inhibitors of cytochrome P450 isoforms. Drug Metab Dispos 25:853-862. (Pubitemid 27318604)
21. Landahl S, Andersson T, Larsson M, Lernfeldt B, Lundborg P, Regårdh CG, Sixt E, and Skånberg I (1992) Pharmacokinetic study of omeprazole in elderly healthy volunteers. Clin Pharmacokinet 23:469-476.
22. Lefebvre RA, Flouvat B, Karolac-Tamisier S, Moerman E, and Van Ganse E (1992) Influence of lansoprazole treatment on diazepam plasma concentrations. Clin Pharmacol Ther 52:458-463.
23. Li XQ, Andersson TB, Ahlström M, and Weidolf L (2004) Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos 32:821-827. (Pubitemid 38955611)
24. Li XQ, Weidolf L, Simonsson R, and Andersson TB (2005) Enantiomer/enantiomer interactions between the S- and R-isomers of omeprazole in human cytochrome P450 enzymes: major role of CYP2C19 and CYP3A4. J Pharmacol Exp Ther 315:777-787. (Pubitemid 41500744)
25. Liu KH, Kim MJ, Shon JH, Moon YS, Seol SY, Kang W, Cha IJ, and Shin JG (2005) Stereoselective inhibition of cytochrome P450 forms by lansoprazole and omeprazole in vitro. Xenobiotica 35:27-38. (Pubitemid 40459215)
26. Liu TJ and Jackevicius CA (2010) Drug interaction between clopidogrel and proton pump inhibitors. Pharmacotherapy 30:275-289.
27. Malling D, Poulsen MN, and Søgaard B (2005) The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects. Br J Clin Pharmacol 60:287-290. (Pubitemid 41224136)
28. Nishiya Y, Hagihara K, Kurihara A, Okudaira N, Farid NA, Okazaki O, and Ikeda T (2009) Comparison of mechanism-based inhibition of human cytochrome P450 2C19 by ticlopidine, clopidogrel, and prasugrel. Xenobiotica 39:836-843.
29. Ogawa R and Echizen H (2010) Drug-drug interaction profiles of proton pump inhibitors. Clin Pharmacokinet 49:509-533.
30. Ogilvie BW, Yerino P, Kazmi F, Buckley DB, Rostami-Hodjegan A, Paris BL, Toren P, and Parkinson A (2011) The proton pump inhibitor, omeprazole, but not lansoprazole or pantoprazole, is a metabolism-dependent inhibitor of CYP2C19: implications for coadministration with clopidogrel. Drug Metab Dispos 39:2020-2033.
31. Ohbuchi M, Noguchi K, Kawamura A, and Usui T (2012) Different effects of proton pump inhibitors and famotidine on the clopidogrel metabolic activation by recombinant CYP2B6, CYP2C19 and CYP3A4. Xenobiotica 42:633-640.
32. Oyetayo OO and Talbert RL (2010) Proton pump inhibitors and clopidogrel: is it a significant drug interaction? Expert Opin Drug Saf 9:593-602.
33. Pue MA, Laroche J, Meineke I, and de Mey C (1993) Pharmacokinetics of pantoprazole following single intravenous and oral administration to healthy male subjects. Eur J Clin Pharmacol 44:575-578. (Pubitemid 23197845)
34. Rassen JA, Choudhry NK, Avorn J, and Schneeweiss S (2009) Cardiovascular outcomes and mortality in patients using clopidogrel with proton pump inhibitors after percutaneous coronary intervention or acute coronary syndrome. Circulation 120:2322-2329.
35. Ray WA, Murray KT, Griffin MR, Chung CP, Smalley WE, Hall K, Daugherty JR, Kaltenbach LA, and Stein CM (2010) Outcomes with concurrent use of clopidogrel and proton-pump inhibitors: a cohort study. Ann Intern Med 152:337-345.
36. Setoyama T, Laurent A, Humphries T, and Hasegawa J (2005) Pharmacokinetics of rabeprazole following single intravenous and oral administration to healthy subjects. Int J Clin Pharmacol Ther 43:37-42. (Pubitemid 40123995)
37. Shah BS, Parmar SA, Mahajan S, and Mehta AA (2012) An insight into the interaction between clopidogrel and proton pump inhibitors. Curr Drug Metab 13:225-235.
38. Shi S and Klotz U (2008) Proton pump inhibitors: an update of their clinical use and pharmacokinetics. Eur J Clin Pharmacol 64:935-951.
39. Shmulevich E, Friger M, Gilutz H, and Azab AN (2011) Clopidogrel and proton pump inhibitors: is there a significant drug-drug interaction? Can J Cardiovasc Nurs 21:27-36.
40. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, Gibson Q, et al. (2009) Association of cytochrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA 302:849-857.
41. Uno T, Sugimoto K, Sugawara K, and Tateishi T (2008) The role of cytochrome P4502C19 in R-warfarin pharmacokinetics and its interaction with omeprazole. Ther Drug Monit 30:276-281.
42. Vakily M, Lee RD, Wu J, Gunawardhana L, and Mulford D (2009) Drug interaction studies with dexlansoprazole modified release (TAK-390MR), a proton pump inhibitor with a dual delayed-release formulation: results of four randomized, double-blind, crossover, placebocontrolled, single-centre studies. Clin Drug Investig 29:35-50.
43. VandenBranden M, Ring BJ, Binkley SN, and Wrighton SA (1996) Interaction of human liver cytochromes P450 in vitro with LY307640, a gastric proton pump inhibitor. Pharmacogenetics 6:81-91. (Pubitemid 26097628)
44. Venkatakrishnan K and Obach RS (2007) Drug-drug interactions via mechanism-based cytochrome P450 inactivation: points to consider for risk assessment from in vitro data and clinical pharmacologic evaluation. Curr Drug Metab 8:449-462. (Pubitemid 47603409)
45. Vuppugalla R, Kim S, Zvyaga T, Han YH, Balimane P, Marathe P, and Rodrigues AD (2010) Anticipating and minimizing drug interactions in a drug discovery and development setting: an industrial perspective, in Enzyme- and Transporter-Based Drug-Drug Interactions: Progress and Future Challenges (Pang KS, Rodrigues AD, Peter RM, eds), pp 585-624, Springer, New York.
46. Walsky RL and Obach RS (2004) Validated assays for human cytochrome P450 activities. Drug Metab Dispos 32:647-660.
47. Walsky RL, Gaman EA, and Obach RS (2005) Examination of 209 drugs for inhibition of cytochrome P450 2C8. J Clin Pharmacol 45:68-78.
48. Walsky RL, Astuccio AV, and Obach RS (2006) Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6. J Clin Pharmacol 46:1426-1438. (Pubitemid 44704203)
49. m diazepam N-demethylase in livers of poor metabolizers for S-mephenytoin 4′-hydroxylation. Pharmacogenetics 4:323-331.
50. Yu KS, Yim DS, Cho JY, Park SS, Park JY, Lee KH, Jang IJ, Yi SY, Bae KS, and Shin SG (2001) Effect of omeprazole on the pharmacokinetics of moclobemide according to the genetic polymorphism of CYP2C19. Clin Pharmacol Ther 69:266-273. (Pubitemid 32382510)
51. Zhang H, Ragueneau-Majlessi I, and Levy RH (2009) Interaction between clopidogrel and proton pump inhibitors: hypothesis to explain multifactorial CYP2C19 inhibition. Drug Metab Lett 3:287-289.