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Drug Discovery Case History

The discovery and development of prasugrel

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Pages 897-905 | Published online: 24 Apr 2013

Bibliography

  • Ruggeri ZM. Platelets in atherothrombosis. Nat Med 2002;8:1227-34
  • Huo Y, Ley KF. Role of platelets in the development of atherosclerosis. Trends Cardiovasc Med 2004;14:18-22
  • Abbracchio MP, Boeynaems JM, Barnard EA, et al. Characterization of the UDP-glucose receptor (re-named here the P2Y14 receptor) adds diversity to the P2Y receptor family. Trends Pharmacol Sci 2003;24:52-5
  • Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature 1962;194:927-9
  • Jin J, Daniel JL, Kunapuli SP. Molecular basis for ADP-induced platelet activation. II. The P2Y1 receptor mediates ADP-induced intracellular calcium mobilization and shape change in platelets. J Biol Chem 1998;273:2030-4
  • Dorsam RT, Kunapuli SP. Central role of the P2Y12 receptor in platelet activation. J Clin Invest 2004;113:340-5
  • Abbracchio MP, Burnstock G, Boeynaems JM, et al. International Union of Pharmacology LVIII: update on the P2Y G protein-coupled nucleotide receptors: from molecular mechanisms and pathophysiology to therapy. Pharmacol Rev 2006;58:281-341
  • Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001;409:202-7
  • Conley PB, Delaney SM. Scientific and therapeutic insights into the role of the platelet P2Y12 receptor in thrombosis. Curr Opin Hematol 2003;10:333-8
  • Foster CJ, Prosser DM, Agans JM, et al. Molecular identification and characterization of the platelet ADP receptor targeted by thienopyridine antithrombotic drugs. J Clin Invest 2001;107:1591-8
  • Sabatine MS, Cannon CP, Gibson CM, et al. Effect of clopidogrel pretreatment before percutaneous coronary intervention in patients with ST-elevation myocardial infarction treated with fibrinolytics: the PCI-CLARITY study. JAMA 2005;294:1224-32
  • Sabatine MS, Cannon CP, Gibson CM, et al. Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med 2005;352:1179-89
  • Mehta SR, Yusuf S, Peters RJ, et al. Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study. Lancet 2001;358:527-33
  • CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet 1996;348:1329-39
  • Leon MB, Baim DS, Popma JJ, et al. A clinical trial comparing three antithrombotic-drug regimens after coronary-artery stenting. Stent Anticoagulation Restenosis Study Investigators. N Engl J Med 1998;339:1665-71
  • Yusuf S, Fox KAA, Tognoni G, Mehta SR. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001;345:494-502
  • Kurihara A, Hagihara K, Kazui M, et al. In vitro metabolism of antiplatelet agent clopidogrel: cytochrome P450 isoforms responsible for two oxidation steps involved in the active metabolite formation. Drug Metab Rev 2005;37:99
  • Lins R, Broekhuysen J, Necciari J, Deroubaix X. Pharmacokinetic profile of C-14-labeled clopidogrel. Semin Thromb Hemost 1999;25:29-33
  • Hagihara K, Kazui M, Yoshike M, et al. A Possible Mechanism of poorer and more variable response to clopidogrel than prasugrel. Circulation 2008;118:S820-S20
  • Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000;84:891-6
  • Ferreiro JL, Angiolillo DJ. Clopidogrel response variability: current status and future directions. Thromb Haemost 2009;102:7-14
  • Angiolillo DJ, Fernandez-Ortiz A, Bernardo E, et al. Variability in individual responsiveness to clopidogrel: clinical implications, management, and future perspectives. J Am Coll Cardiol 2007;49:1505-16
  • Karazniewicz-Lada M, Danielak D, Glowka F. Genetic and non-genetic factors affecting the response to clopidogrel therapy. Expert Opin Pharmacother 2012;13:663-83
  • Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007;5:2429-36
  • Lee JM, Park S, Shin D-J, et al. Relation of Genetic Polymorphisms in the cytochrome P450 gene with clopidogrel resistance after drug-eluting stent implantation in Koreans. Am J Cardiol 2009;104:46-51
  • Roden DM, Stein CM. Clopidogrel and the concept of high-risk pharmacokinetics. Circulation 2009;119:2127-30
  • De Miguel A, Ibanez B, Badimon JJ. Clinical implications of clopidogrel resistance. Thromb Haemost 2008;100:196-203
  • Vivas D, Angiolillo DJ. Platelet P2Y(1)(2) receptor inhibition: an update on clinical drug development. Am J Cardiovasc Drugs 2010;10:217-26
  • Jakubowski JA, Payne CD, Brandt JT, et al. The platelet inhibitory effects and pharmacokinetics of prasugrel after administration of loading and maintenance doses in healthy subjects. J Cardiovasc Pharmacol 2006;47:377-84
  • Wallentin L, Varenhorst C, James S, et al. Prasugrel achieves greater and faster P2Y12receptor-mediated platelet inhibition than clopidogrel due to more efficient generation of its active metabolite in aspirin-treated patients with coronary artery disease. Eur Heart J 2008;29:21-30
  • Jernberg T, Payne CD, Winters KJ, 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;27:1166-73
  • Montalescot G, Wiviott SD, 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;373:723-31
  • Wiviott SD, Antman EM, Winters KJ, et al. Randomized comparison of prasugrel (CS-747, LY640315), a novel thienopyridine P2Y12 antagonist, with clopidogrel in percutaneous coronary intervention: results of the Joint Utilization of Medications to Block Platelets Optimally (JUMBO)-TIMI 26 trial. Circulation 2005;111:3366-73
  • Koike H, Asai F, Sugidachi A, et al. Preparation of substituted hydrothienopyridine derivatives having antithrombotic activity. CA2077695; 1993
  • Sugidachi A, Asai F, Ogawa T, et al. The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties. Br J Pharmacol 2000;129:1439-46
  • Sugidachi A, Asai F, Yoneda K, et al. Antiplatelet action of R-99224, an active metabolite of a novel thienopyridine-type G(i)-linked P2T antagonist, CS-747. Br J Pharmacol 2001;132(1):47-54
  • Smith RL, Gillespie TA, Rash TJ, et al. Disposition and metabolic fate of prasugrel in mice, rats, and dogs. Xenobiotica 2007;37:884-901
  • Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos 2007;35:1096-104
  • Williams ET, Jones KO, Ponsler GD, et al. The biotransformation of prasugrel, a new thienopyridine prodrug, by the human carboxylesterases 1 and 2. Drug Metab Dispos 2008;36:1227-32
  • Farid NA, McIntosh M, Garofolo F, et al. Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/tandem mass spectrometry. Rapid Commun Mass Spectrom 2007;21:169-79
  • Rehmel JL, Eckstein JA, Farid NA, et al. Interactions of two major metabolites of prasugrel, a thienopyridine antiplatelet agent, with the cytochromes P450. Drug Metab Dispos 2006;34:600-7
  • Algaier I, Jakubowski JA, 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;6:1908-14
  • Farid NA, Kurihara A, Wrighton SA. Metabolism and disposition of the thienopyridine antiplatelet drugs ticlopidine, clopidogrel, and prasugrel in humans. J Clin Pharmacol 2010;50:126-42
  • Payne CD, Li YG, Small DS, et al. Increased active metabolite formation explains the greater platelet inhibition with prasugrel compared to high-dose clopidogrel. J Cardiovasc Pharmacol 2007;50:555-62
  • Wallentin L. P2Y(12) inhibitors: differences in properties and mechanisms of action and potential consequences for clinical use. Eur Heart J 2009;30:1964-77
  • Brandt JT, Payne CD, Wiviott SD, 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; e9-16
  • Dansette PM, Rosi J, Debernardi J, et al. Metabolic activation of prasugrel: nature of the two competitive pathways resulting in the opening of its thiophene ring. Chem Res Toxicol 2012;25:1058-65
  • Dansette PM, Thebault S, Bertho G, Mansuy D. Formation and fate of a sulfenic acid intermediate in the metabolic activation of the antithrombotic prodrug prasugrel. Chem Res Toxicol 2010;23:1268-74
  • Takahashi M, Kawabata K, Kurihara A. Chiral inversion and enantioselective active metabolite formation of prasugrel, a novel thienopyridine antiplatelet agent, in dogs. Drug Metab Rev 2006;38:88-9
  • Hasegawa M, Sugidachi A, Ogawa T, et al. Stereoselective inhibition of human platelet aggregation by R-138727, the active metabolite of CS-747 (prasugrel, LY640315), a novel P2Y12 receptor inhibitor. Thromb Haemost 2005;94:593-8
  • Wickremsinhe ER, Tian Y, Ruterbories KJ, et al. Stereoselective metabolism of prasugrel in humans using a novel chiral liquid chromatography-tandem mass spectrometry method. Drug Metab Dispos 2007;35:917-21
  • Jakubowski JA, Winters KJ, Naganuma H, Wallentin L. Prasugrel: a novel thienopyridine antiplatelet agent. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev 2007;25:357-74
  • Niitsu Y, Jakubowski JA, Sugidachi A, Asai F. Pharmacology of CS-747 (prasugrel, LY640315), a novel, potent antiplatelet agent with in vivo P2Y12 receptor antagonist activity. Semin Thromb Hemost 2005;31:184-94
  • 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;5:1545-51
  • Mega JL, Close SL, Wiviott SD, et al. Genetic variants in ABCB1 and CYP2C19 and cardiovascular outcomes after treatment with clopidogrel and prasugrel in the TRITON-TIMI 38 trial: a pharmacogenetic analysis. Lancet 2010;376:1312-19
  • Yin T, Miyata T. Pharmacogenomics of clopidogrel: evidence and perspectives. Thromb Res 2011;128:307-16
  • Frere C, Cuisset T, Gaborit B, et al. The CYP2C19*17 allele is associated with better platelet response to clopidogrel in patients admitted for non-ST acute coronary syndrome. J Thromb Haemost 2009;7:1409-11
  • 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;30:1744-52
  • Brandt JT, Close SL, Iturria SJ, et al. Common polymorphisms of CYP2C19 and CYP2C9 affect the pharmacokinetic and pharmacodynamic response to clopidogrel but not prasugrel. J Thromb Haemost 2007;5:2429-36
  • Mega JL, Close SL, Wiviott SD, et al. Cytochrome P450 genetic polymorphisms and the response to prasugrel: relationship to pharmacokinetic, pharmacodynamic, and clinical outcomes. Circulation 2009;119:2553-60
  • Bhatt DL, Scheiman J, Abraham NS, et al. ACCF/ACG/AHA 2008 Expert consensus document on reducing the gastrointestinal risks of antiplatelet therapy and NSAID use a report of the American college of cardiology foundation task force on clinical expert consensus documents. J Am Coll Cardiol 2008;52:1502-17
  • Suh JW, Koo BK, Zhang SY, et al. Increased risk of atherothrombotic events associated with cytochrome P450 3A5 polymorphism in patients taking clopidogrel. Can Med Assoc J 2006;174:1715-22
  • Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump inhibitors following acute coronary syndrome. JAMA 2009;301:937-44
  • Shah BS, Parmar SA, Mahajan S, Mehta AA. An insight into the interaction between clopidogrel and proton pump inhibitors. Curr Drug Metab 2012;13:225-35
  • Sibbing D, Morath T, Stegherr J, et al. Impact of proton pump inhibitors on the antiplatelet effects of clopidogrel. Thromb Haemost 2009;101:714-19
  • O'Donoghue ML, Braunwald E, Antman EM, 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;374:989-97
  • Small DS, Farid NA, Payne CD, et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol 2008;48:475-84
  • Daali Y, Ancrenaz V, Bosilkovska M, et al. Ritonavir inhibits the two main prasugrel bioactivation pathways in vitro: a potential drug-drug interaction in HIV patients. Metabolism 2011;60:1584-9
  • Farid NA, Payne CD, Small DS, et al. Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther 2007;81:735-41
  • Farid NA, Small DS, Payne CD, et al. Effect of atorvastatin on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy 2008;28:1483-94
  • Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-15
  • Wiviott SD, Braunwald E, Angiolillo DJ, 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;118:1626-36
  • Roe MT, Armstrong PW, Fox KA, et al. Prasugrel versus clopidogrel for acute coronary syndromes without revascularization. N Engl J Med 2012;367:1297-309
  • Gurbel PA, Erlinge D, Ohman EM, et al. Platelet function during extended prasugrel and clopidogrel therapy for patients with ACS treated without revascularization: the TRILOGY ACS platelet function substudy. JAMA 2012;308:1785-94

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