Pharmacokinetic basis of the antiplatelet action of prasugrel

Fundamental and Clinical Pharmacology

Volumn 26, Issue 1, 2012, Pages 39-46

  Schrör, Karsten ^a   Siller Matula, Jolanta M ^b   Huber, Kurt ^b  

^a UNIVERSITY HOSPITAL DÜSSELDORF   (Germany)

^b MEDICAL UNIVERSITY OF VIENNA   (Austria)

Author keywords

Antiplatelet drugs; Clopidogrel; CYP P450 isozymes; Platelet aggregation; Prasugrel; Response variability

Indexed keywords

ACETYLSALICYLIC ACID; CARBOXYLESTERASE; CLOPIDOGREL; CYTOCHROME P450 2B6; CYTOCHROME P450 2C19; CYTOCHROME P450 2C9; CYTOCHROME P450 3A4; OMEPRAZOLE; PRASUGREL; PROTON PUMP INHIBITOR; THIENOPYRIDINE DERIVATIVE; THIOLACTONE; TICLOPIDINE;

ANTICOAGULATION; DNA POLYMORPHISM; DRUG HALF LIFE; DRUG METABOLISM; ENZYME ACTIVITY; GENE EXPRESSION; HUMAN; IN VITRO STUDY; IN VIVO STUDY; INTESTINE; LIPOPHILICITY; MAXIMUM PLASMA CONCENTRATION; PRIORITY JOURNAL; REVIEW; THROMBOCYTE AGGREGATION;

ADMINISTRATION, ORAL; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; PIPERAZINES; PLATELET AGGREGATION INHIBITORS; PRODRUGS; PURINERGIC P2Y RECEPTOR ANTAGONISTS; THIOPHENES;

EID: 84855704861     PISSN: 07673981     EISSN: 14728206     Source Type: Journal    
DOI: 10.1111/j.1472-8206.2011.00986.x     Document Type: Review

References (54)

1. Hochholzer W., Trenk D., Frundi D. et al. Time dependence of platelet inhibition after a 600-mg loading dose of clopidogrel in a large, unselected cohort of candidates for percutaneous coronary intervention. Circulation (2005) 111 2560-2564.
2. von Beckerath N., Taubert D., Pogatsa-Murray G., Schomig E., Kastrati A., Schomig A. Absorption, metabolization, and antiplatelet effects of 300-, 600-, and 900-mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intracoronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation (2005) 112 2946-2950.
3. Matetzky S., Shenkman B., Guetta V. et al. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation (2004) 109 3171-3175.
4. Bliden K.P., DiChiara J., Tantry U.S., Bassi A.K., Chaganti S.K., Gurbel P.A. Increased risk in patients with high platelet aggregation receiving chronic clopidogrel therapy undergoing percutaneous coronary intervention: is the current antiplatelet therapy adequate? J. Am. Coll. Cardiol. (2007) 49 657-666.
5. Siller-Matula J., Schror K., Wojta J., Huber K. Thienopyridines in cardiovascular disease: focus on clopidogrel resistance. Thromb. Haemost. (2007) 97 385-393.
6. Geisler T., Langer H., Wydymus M. et al. Low response to clopidogrel is associated with cardiovascular outcome after coronary stent implantation. Eur. Heart J. (2006) 27 2420-2425.
7. Wiviott S.D., Braunwald E., McCabe C.H. et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N. Engl. J. Med. (2007) 357 2001-2015.
8. Wiviott S.D., Braunwald E., Angiolillo D.J. et al. Greater clinical benefit of more intensive oral antiplatelet therapy with prasugrel in patients with diabetes mellitus in the trial to assess improvement in therapeutic outcomes by optimizing platelet inhibition with prasugrel-Thrombolysis in Myocardial Infarction 38. Circulation (2008) 118 1626-1636.
9. Payne C.D., Li Y.G., Small D.S. et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J. Cardiovasc. Pharmacol. (2007) 50 555-562.
10. Sugidachi A., Ogawa T., Kurihara A. et al. The greater in vivo antiplatelet effects of prasugrel as compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to that of clopidogrel's active metabolite. J. Thromb. Haemost. (2007) 5 1545-1551.
11. Farid N.A., Kurihara A., Wrighton S.A. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J. Clin. Pharmacol. (2010) 50 126-142.
12. Farid N.A., Smith R.L., Gillespie T.A. et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab. Dispos. (2007) 35 1096-1104.
13. Tang M., Mukundan M., Yang J. et al. Antiplatelet agents aspirin and clopidogrel are hydrolyzed by distinct carboxylesterases, and clopidogrel is transesterificated in the presence of ethyl alcohol. J. Pharmacol. Exp. Ther. (2006) 319, 1467-1476.
14. Taubert D., Kastrati A., Harlfinger S. et al. Pharmacokinetics of clopidogrel after administration of a high loading dose. Thromb. Haemost. (2004) 92 311-316.
15. Patel A., Jones S.A., Ferro A., Patel N. Pharmaceutical salts: a formulation trick or a clinical conundrum? Br. J. Cardiol. (2009) 16 281-286.
16. Verbeeck R.K., Kanfer I., Walker R.B. Generic substitution: the use of medicinal products containing different salts and implications for safety and efficacy. Eur J Pharm Sci. (2006) 28 1-6.
17. Hagihara K., Kazui M., Ikenaga H. et al. Comparison of formation of thiolactones and active metabolites of prasugrel and clopidogrel in rats and dogs. Xenobiotica (2009) 39 218-226.
18. Zanger U.M., Turpeinen M., Klein K., Schwab M. Functional pharmacogenetics/genomics of human cytochromes P450 involved in drug biotransformation. Anal. Bioanal. Chem. (2008) 392 1093-1108.
19. Chen X.P., Tan Z.R., Huang S.L., Huang Z., Ou-Yang D.S., Zhou H.H. Isozyme-specific induction of low-dose aspirin on cytochrome P450 in healthy subjects. Clin. Pharmacol. Ther. (2003) 73 264-271.
20. Rehmel J.L., Eckstein J.A., Farid N.A. et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab. Dispos. (2006) 34 600-607.
21. Gorchakova O., von Beckerath N., Gawaz M. et al. Antiplatelet effects of a 600mg loading dose of clopidogrel are not attenuated in patients receiving atorvastatin or simvastatin for at least 4weeks prior to coronary artery stenting. Eur. Heart J. (2004) 25 1898-1902.
22. Lim M.J., Spencer F.A., Gore J.M. et al. Impact of combined pharmacologic treatment with clopidogrel and a statin on outcomes of patients with non-ST-segment elevation acute coronary syndromes: perspectives from a large multinational registry. Eur. Heart J. (2005) 26 1063-1069.
23. Farid N.A., Payne C.D., Small D.S. et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin. Pharmacol. Ther. (2007) 81 735-741.
24. Small D.S., Farid N.A., Li Y.G. et al. Effect of ranitidine on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. Curr. Med. Res. Opin. (2008) 24 2251-2257.
25. Brandt J.T., Close S.L., Iturria S.J. et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J. Thromb. Haemost. (2007) 5 2429-2436.
26. Trenk D., Hochholzer W., Fromm M.F. et al. Cytochrome P450 2C19 681G>A polymorphism and high on-clopidogrel platelet reactivity associated with adverse 1-year clinical outcome of elective percutaneous coronary intervention with drug-eluting or bare-metal stents. J. Am. Coll. Cardiol. (2008) 51 1925-1934.
27. Sibbing D., Morath T., Stegherr J. et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb. Haemost. (2009) 101 714-719.
28. Varenhorst C., James S., Erlinge D. et al. Genetic variation of CYP2C19 affects both pharmacokinetic and pharmacodynamic responses to clopidogrel but not prasugrel in aspirin-treated patients with coronary artery disease. Eur. Heart J. (2009) 30 1744-1752.
29. Collet J.P., Hulot J.S., Pena A. et al. Cytochrome P450 2C19 polymorphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet (2009) 373 309-317.
30. Mega J.L., Close S.L., Wiviott S.D. et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation (2009) 119 2553-2560.
31. Wallentin L. P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur. Heart J. (2009) 30 1964-1977.
32. Ho P.M., Maddox T.M., Wang L. et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA (2009) 301 937-944.
33. Siller-Matula J.M., Spiel A.O., Lang I.M., Kreiner G., Christ G., Jilma B. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am. Heart J. (2009) 157 148-e1.
34. Gilard M., Arnaud B., Cornily J.C. et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the randomized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J. Am. Coll. Cardiol. (2008) 51 256-260.
35. Laine L., Hennekens C. Proton pump inhibitor and clopidogrel interaction: fact or fiction? Am. J. Gastroenterol. (2010) 105 34-41.
36. O'Donoghue M.L., Braunwald E., Antman E.M. et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet (2009) 374 989-997.
37. Siller-Matula J.M., Jilma B., Schror K., Christ G., Huber K. Effect of proton pump inhibitors on clinical outcome in patients treated with clopidogrel: a systematic review and meta-analysis. J. Thromb. Haemost. (2010) 8 2624-2641.
38. Richter T., Murdter T.E., Heinkele G. et al. Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine. J. Pharmacol. Exp. Ther. (2004) 308 189-197.
39. Turpeinen M., Tolonen A., Uusitalo J., Jalonen J., Pelkonen O., Laine K. Effect of clopidogrel and ticlopidine on cytochrome P450 2B6 activity as measured by bupropion hydroxylation. Clin. Pharmacol. Ther. (2005) 77 553-559.
40. Farid N.A., Payne C.D., Ernest C.S. II et al. Prasugrel, a new thienopyridine antiplatelet drug, weakly inhibits cytochrome P450 2B6 in humans. J. Clin. Pharmacol. (2008) 48 53-59.
41. Hagihara K., Nishiya Y., Kurihara A., Kazui M., Farid N.A., Ikeda T. Comparison of human cytochrome P450 inhibition by the thienopyridines prasugrel, clopidogrel, and ticlopidine. Drug Metab Pharmacokinet. (2008) 23 412-420.
42. Nishiya Y., Hagihara K., Ito T. et al. Mechanism-based inhibition of human cytochrome P450 2B6 by ticlopidine, clopidogrel, and the thiolactone metabolite of prasugrel. Drug Metab. Dispos. (2009) 37 589-593.
43. Ding Z., Kim S., Dorsam R.T., Jin J., Kunapuli S.P. Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270. Blood (2003) 101 3908-3914.
44. Algaier I., Jakubowski J.A., Asai F., von Kugelgen I. Interaction of the active metabolite of prasugrel, R-138727, with cysteine 97 and cysteine 175 of the human P2Y12 receptor. J. Thromb. Haemost. (2008) 6 1908-1914.
45. Brandt J.T., Payne C.D., Wiviott S.D. et al. A comparison of prasugrel and clopidogrel loading doses on platelet function: magnitude of platelet inhibition is related to active metabolite formation. Am. Heart J. (2007) 153 66.e9-66.e16.
46. Jernberg T., Payne C.D., Winters K.J. et al. Prasugrel achieves greater inhibition of platelet aggregation and a lower rate of non-responders compared with clopidogrel in aspirin-treated patients with stable coronary artery disease. Eur. Heart J. (2006) 27 1166-1173.
47. Bonello L., Camoin-Jau L., Armero S. et al. Tailored clopidogrel loading dose according to platelet reactivity monitoring to prevent acute and subacute stent thrombosis. Am. J. Cardiol. (2009) 103 5-10.
48. Storey R.F., Husted S., Harrington R.A. et al. Inhibition of platelet aggregation by AZD6140, a reversible oral P2Y12 receptor antagonist, compared with clopidogrel in patients with acute coronary syndromes. J. Am. Coll. Cardiol. (2007) 50 1852-1856.
49. Jakubowski J.A., Matsushima N., Asai F. et al. A multiple dose study of prasugrel (CS-747), a novel thienopyridine P2Y12 inhibitor, compared with clopidogrel in healthy humans. Br. J. Clin. Pharmacol. (2007) 63 421-430.
50. Cuisset T., Frere C., Quilici J. et al. Benefit of a 600-mg loading dose of clopidogrel on platelet reactivity and clinical outcomes in patients with non-ST-segment elevation acute coronary syndrome undergoing coronary stenting. J. Am. Coll. Cardiol. (2006) 48 1339-1345.
51. Collet J.P., Silvain J., Landivier A. et al. Dose effect of clopidogrel reloading in patients already on 75-mg maintenance dose: the Reload with Clopidogrel Before Coronary Angioplasty in Subjects Treated Long Term with Dual Antiplatelet Therapy (RELOAD) study. Circulation (2008) 118 1225-1233.
52. Neubauer H., Kruger J.C., Lask S. et al. Comparing the antiplatelet effect of clopidogrel hydrogensulfate and clopidogrel besylate: a crossover study. Clin. Res. Cardiol. (2009) 98 533-540.
53. Montalescot G., Wiviott S.D., Braunwald E. et al. Prasugrel compared with clopidogrel in patients undergoing percutaneous coronary intervention for ST-elevation myocardial infarction (TRITON-TIMI 38): double-blind, randomised controlled trial. Lancet (2009) 373 723-731.
54. Murphy S.A., Antman E.M., Wiviott S.D. et al. Reduction in recurrent cardiovascular events with prasugrel compared with clopidogrel in patients with acute coronary syndromes from the TRITON-TIMI 38 trial. Eur. Heart J. (2008) 29 2473-2479.