Carboxylesterase 1 as a determinant of clopidogrel metabolism and activations

Journal of Pharmacology and Experimental Therapeutics

Volumn 344, Issue 3, 2013, Pages 665-672

  Zhu, Hao Jie ^a,b   Wang, Xinwen ^a,c   Gawronski, Brian E ^a   Brinda, Bryan J ^a   Angiolillo, Dominick J ^a   Markowitz, John S ^a,b  

^a Department of Pharmacotherapy and Translational Research ^*  (United States)

^b UNIVERSITY OF FLORIDA   (United States)

^c CHINA PHARMACEUTICAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

2 BROMO 3' METHOXY ACETOPHENONE; 2 OXO CLOPIDOGREL; BIS(4 NITROPHENYL) PHOSPHATE; CARBOXYLESTERASE; CARBOXYLESTERASE 1; CARBOXYLIC ACID; CLOPIDOGREL; DRUG METABOLITE; UNCLASSIFIED DRUG;

AREA UNDER THE CURVE; ARTICLE; CATALYSIS; CELL FRACTIONATION; CES1 GENE; COMPLEX FORMATION; CONTROLLED STUDY; DRUG ACTIVATION; DRUG BLOOD LEVEL; DRUG HYDROLYSIS; DRUG LIVER LEVEL; DRUG MECHANISM; DRUG METABOLISM; DRUG TRANSFORMATION; ENZYME ACTIVITY; ENZYME INHIBITION; GENE; GENE FUNCTION; GENETIC ASSOCIATION; GENETIC POLYMORPHISM; GENETIC VARIABILITY; HUMAN; HUMAN TISSUE; IN VITRO STUDY; METABOLITE; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; TREATMENT RESPONSE;

BIOTRANSFORMATION; CARBOXYLIC ESTER HYDROLASES; CELL LINE; HUMANS; HYDROLYSIS; LIVER; NITROPHENOLS; PLATELET AGGREGATION INHIBITORS; POLYMORPHISM, GENETIC; TICLOPIDINE;

EID: 84874423935     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.112.201640     Document Type: Article

References (42)

1. Angiolillo DJ, Bernardo E, Sabaté M, Jimenez-Quevedo P, Costa MA, Palazuelos J, Hernández-Antolin R, Moreno R, Escaned J, and Alfonso F, et al. (2007) Impact of platelet reactivity on cardiovascular outcomes in patients with type 2 diabetes mellitus and coronary artery disease. J Am Coll Cardiol 50:1541-1547.
2. Bouman HJ, Schömig E, van Werkum JW, Velder J, Hackeng CM, Hirschhäuser C, Waldmann C, Schmalz HG, ten Berg JM, and Taubert D (2011) Paraoxonase-1 is a major determinant of clopidogrel efficacy. Nat Med 17:110-116.
3. Bruxel EM, Salatino-Oliveira A, Genro JP, Zeni CP, Polanczyk GV, Chazan R, Rohde LA, and Hutz MH (2012) Association of a carboxylesterase 1 polymorphism with appetite reduction in children and adolescents with attention-deficit/ hyperactivity disorder treated with methylphenidate. Pharmacogenomics J DOI: 10.1038/ tpj.2012.25 [published ahead of print].
4. Ferreiro JL, Sibbing D, and Angiolillo DJ (2010) Platelet function testing and risk of bleeding complications. Thromb Haemost 103:1128-1135.
5. Fukami T, Nakajima M, Maruichi T, Takahashi S, Takamiya M, Aoki Y, McLeod HL, and Yokoi T (2008) Structure and characterization of human carboxylesterase 1A1, 1A2, and 1A3 genes. Pharmacogenet Genomics 18:911-920.
6. Fukami T, Takahashi S, Nakagawa N, Maruichi T, Nakajima M, and Yokoi T (2010) In vitro evaluation of inhibitory effects of antidiabetic and antihyperlipidemic drugs on human carboxylesterase activities. Drug Metab Dispos 38:2173-2178.
7. Geshi E, Kimura T, Yoshimura M, Suzuki H, Koba S, Sakai T, Saito T, Koga A, Muramatsu M, and Katagiri T (2005) A single nucleotide polymorphism in the carboxylesterase gene is associated with the responsiveness to imidapril medication and the promoter activity. Hypertens Res 28:719-725.
8. 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.
9. Hatfield MJ and Potter PM (2011) Carboxylesterase inhibitors. Expert Opin Ther Pat 21:1159-1171.
10. Hosokawa M, Endo T, Fujisawa M, Hara S, Iwata N, Sato Y, and Satoh T (1995) Interindividual variation in carboxylesterase levels in human liver microsomes. Drug Metab Dispos 23:1022-1027.
11. Hosokawa M, Furihata T, Yaginuma Y, Yamamoto N, Koyano N, Fujii A, Nagahara Y, Satoh T, and Chiba K (2007) Genomic structure and transcriptional regulation of the rat, mouse, and human carboxylesterase genes. Drug Metab Rev 39:1-15.
12. Hosokawa M, Furihata T, Yaginuma Y, Yamamoto N, Watanabe N, Tsukada E, Ohhata Y, Kobayashi K, Satoh T, and Chiba K (2008) Structural organization and characterization of the regulatory element of the human carboxylesterase (CES1A1 and CES1A2) genes. Drug Metab Pharmacokinet 23:73-84.
13. Imai T, Taketani M, Shii M, Hosokawa M, and Chiba K (2006) Substrate specificity of carboxylesterase isozymes and their contribution to hydrolase activity in human liver and small intestine. Drug Metab Dispos 34:1734-1741.
14. Kara-zniewicz-Lada M, Danielak D, and Glówka F (2012) Genetic and non-genetic factors affecting the response to clopidogrel therapy. Expert Opin Pharmacother 13:663-683.
15. 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.
16. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, Chambers CE, Ellis SG, Guyton RA, and Hollenberg SM, et al.; American College of Cardiology Foundation; ; American Heart Association Task Force on Practice Guidelines; ; Society for Cardiovascular Angiography and Interventions (2011) 2011 ACCF/ AHA/SCAI Guideline for Percutaneous Coronary Intervention. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines and the Society for Cardiovascular Angiography and Interventions. J Am Coll Cardiol 58:e44-e122.
17. Lewis JP, Horenstein RB, Ryan K, O'Connell JR, Gibson Q, Mitchell BD, Tanner K, Chai S, Bliden KP, and Tantry US, et al. (2013) The functional G143E variant of carboxylesterase 1 is associated with increased clopidogrel active metabolite levels and greater clopidogrel response. Pharmacogenet Genomics 23:1-8.
18. Mega JL, Close SL, Wiviott SD, Shen L, Hockett RD, Brandt JT, Walker JR, Antman EM, Macias W, and Braunwald E, et al. (2009) Cytochrome p-450 polymorphisms and response to clopidogrel. N Engl J Med 360:354-362.
19. Nemoda Z, Angyal N, Tarnok Z, Gadoros J, and Sasvari-Szekely M (2009) Carboxylesterase 1 gene polymorphism and methylphenidate response in ADHD. Neuropharmacology 57:731-733.
20. Patrick KS, Straughn AB, Minhinnett RR, Yeatts SD, Herrin AE, DeVane CL, Malcolm R, Janis GC, and Markowitz JS (2007) Influence of ethanol and gender on methylphenidate pharmacokinetics and pharmacodynamics. Clin Pharmacol Ther 81:346-353.
21. Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, Pascal M, Herbert JM, Maffrand JP, and Picard C (2002) Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metab Dispos 30:1288-1295.
22. Rhoades JA, Peterson YK, Zhu HJ, Appel DI, Peloquin CA, and Markowitz JS (2012) Prediction and in vitro evaluation of selected protease inhibitor antiviral drugs as inhibitors of carboxylesterase 1: A potential source of drug-drug interactions. Pharm Res 29:972-982.
23. Ross MK, Borazjani A, Wang R, Crow JA, and Xie S (2012) Examination of the carboxylesterase phenotype in human liver. Arch Biochem Biophys 522:44-56.
24. Ross MK and Crow JA (2007) Human carboxylesterases and their role in xenobiotic and endobiotic metabolism. J Biochem Mol Toxicol 21:187-196.
25. Sai K, Saito Y, Tatewaki N, Hosokawa M, Kaniwa N, Nishimaki-Mogami T, Naito M, Sawada J, Shirao K, and Hamaguchi T, et al. (2010) Association of carboxylesterase 1A genotypes with irinotecan pharmacokinetics in Japanese cancer patients. Br J Clin Pharmacol 70:222-233.
26. Shi D, Yang D, Prinssen EP, Davies BE, and Yan B (2011) Surge in expression of carboxylesterase 1 during the post-neonatal stage enables a rapid gain of the capacity to activate the anti-influenza prodrug oseltamivir. J Infect Dis 203: 937-942.
27. Shi D, Yang J, Yang D, LeCluyse EL, Black C, You L, Akhlaghi F, and Yan B (2006) Anti-influenza prodrug oseltamivir is activated by carboxylesterase human carboxylesterase 1, and the activation is inhibited by antiplatelet agent clopidogrel. J Pharmacol Exp Ther 319:1477-1484.
28. Shuldiner AR, O'Connell JR, Bliden KP, Gandhi A, Ryan K, Horenstein RB, Damcott CM, Pakyz R, Tantry US, and 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.
29. Takahashi M, Pang H, Kawabata K, Farid NA, and Kurihara A (2008) Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS. J Pharm Biomed Anal 48:1219-1224.
30. Tang M, Mukundan M, Yang J, Charpentier N, LeCluyse EL, Black C, Yang D, Shi D, and Yan B (2006) Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J Pharmacol Exp Ther 319:1467-1476.
31. Tarkiainen EK, Backman JT, Neuvonen M, Neuvonen PJ, Schwab M, and Niemi M (2012) Carboxylesterase 1 polymorphism impairs oseltamivir bioactivation in humans. Clin Pharmacol Ther 92:68-71.
32. Tuffal G, Roy S, Lavisse M, Brasseur D, Schofield J, Delesque Touchard N, Savi P, Bremond N, Rouchon MC, and Hurbin F, et al. (2011) An improved method for specific and quantitative determination of the clopidogrel active metabolite isomers in human plasma. Thromb Haemost 105:696-705.
33. Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE, Jr, Ettinger SM, Fesmire FM, Ganiats TG, Jneid H, and Lincoff AM, et al. (2011) 2011 ACCF/ AHA focused update of the guidelines for the management of patients with unstable angina/non-ST-elevation myocardial infarction (updating the 2007 guideline): A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 123: 2022-2060.
34. Yamada S, Richardson K, Tang M, Halaschek-Wiener J, Cook VJ, Fitzgerald JM, Elwood K, Marra F, and Brooks-Wilson A (2010) Genetic variation in carboxylesterase genes and susceptibility to isoniazid-induced hepatotoxicity. Pharmacogenomics J 10:524-536.
35. Yang D, Pearce RE, Wang X, Gaedigk R, Wan YJ, and Yan B (2009) Human carboxylesterases HCE1 and HCE2: Ontogenic expression, inter-individual variability and differential hydrolysis of oseltamivir, aspirin, deltamethrin and permethrin. Biochem Pharmacol 77:238-247.
36. Yoshimura M, Kimura T, Ishii M, Ishii K, Matsuura T, Geshi E, Hosokawa M, and Muramatsu M (2008) Functional polymorphisms in carboxylesterase1A2 (CES1A2) gene involves specific protein 1 (Sp1) binding sites. Biochem Biophys Res Commun 369:939-942.
37. Zhu HJ, Appel DI, Jiang Y, and Markowitz JS (2009a) Age-and sex-related expression and activity of carboxylesterase 1 and 2 in mouse and human liver. Drug Metab Dispos 37:1819-1825.
38. Zhu HJ, Appel DI, Johnson JA, Chavin KD, and Markowitz JS (2009b) Role of carboxylesterase 1 and impact of natural genetic variants on the hydrolysis of trandolapril. Biochem Pharmacol 77:1266-1272.
39. Zhu HJ, Appel DI, Peterson YK, Wang Z, and Markowitz JS (2010) Identification of selected therapeutic agents as inhibitors of carboxylesterase 1: Potential sources of metabolic drug interactions. Toxicology 270:59-65.
40. ZhuHJ and Markowitz JS (2009) Activation of the antiviral prodrug oseltamivir is impaired by two newly identified carboxylesterase 1 variants. Drug Metab Dispos 37:264-267.
41. Zhu HJ and Markowitz JS (2012) Carboxylesterase 1 (CES1) genetic polymorphisms and oseltamivir activation. Eur J Clin Pharmacol DOI: 10.1007/s00228-012-1350-2 [published ahead of print].
42. Zhu HJ, Patrick KS, Yuan HJ, Wang JS, Donovan JL, DeVane CL, Malcolm R, Johnson JA, Youngblood GL, and Sweet DH, et al. (2008) Two CES1 gene mutations lead to dysfunctional carboxylesterase 1 activity in man: Clinical significance and molecular basis. Am J Hum Genet 82:1241-1248.