ADP receptor-blocker thienopyridines: Chemical structures, mode of action and clinical use. A review

Journal of Invasive Cardiology

Volumn 21, Issue 8, 2009, Pages 406-412

  Hashemzadeh, Mehrnoosh ^a   Goldsberry, Sarah ^d   Furukawa, Matthew ^d   Khoynezhad, Ali ^c   Movahed, Mohammad Reza ^a,b  

^a UNIVERSITY OF ARIZONA   (United States)

^b SOUTHERN ARIZONA VA HEALTH CARE SYSTEM   (United States)

^c UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^d WHITTIER COLLEGE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; ADENOSINE DIPHOSPHATE RECEPTOR; ADENOSINE DIPHOSPHATE RECEPTOR BLOCKING AGENT; ANTITHROMBOCYTIC AGENT; CLOPIDOGREL; DIGOXIN; DRUG METABOLITE; EFFIENT; MEMBRANE RECEPTOR; PRASUGREL; PRODRUG; R 138727; R 95913; RECEPTOR BLOCKING AGENT; THIENOPYRIDINE DERIVATIVE; THIOLACTONE; TICLOPIDINE; UNCLASSIFIED DRUG;

AGRANULOCYTOSIS; APLASTIC ANEMIA; ATHEROSCLEROTIC CARDIOVASCULAR DISEASE; BLEEDING; CLINICAL TRIAL; CYTOPENIA; DRUG ABSORPTION; DRUG EFFICACY; DRUG INDICATION; DRUG MECHANISM; DRUG METABOLISM; DRUG POTENCY; DRUG RECEPTOR BINDING; DRUG SAFETY; DRUG STRUCTURE; DRUG TOLERABILITY; DRUG TRANSFORMATION; GASTROINTESTINAL SYMPTOM; HEART INFARCTION; HUMAN; LIFESPAN; LIVER CELL; LOADING DRUG DOSE; NEUTROPENIA; NONHUMAN; RASH; REVIEW; SKIN BRUISING; STROKE; STRUCTURE ACTIVITY RELATION; THROMBOCYTE MEMBRANE; THROMBOCYTOPENIA; THROMBOSIS; THROMBOTIC THROMBOCYTOPENIC PURPURA; TRANSIENT ISCHEMIC ATTACK; UNSPECIFIED SIDE EFFECT;

CARDIOVASCULAR DISEASES; HUMANS; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PYRIDINES; RECEPTORS, PURINERGIC P2; THROMBOSIS;

EID: 69249096250     PISSN: 10423931     EISSN: 15572501     Source Type: Journal    
DOI: None     Document Type: Review

References (115)

1. Peter K. Principles of Molecular Cardiology. Totowa, New Jersey: Humana Press, 2005.
2. Cazenave JP, Gachet, C. Anti-platelet drugs: Do they affect megakaryocytes? Bailliere's Clinical Haemotology 1997;10:163-180. (Pubitemid 27192461)
3. Savi P, Herbert JM. ADP receptors on platelets and ADP-selective antiaggregating agents. Med Res Rev 1996;16:159-179. (Pubitemid 26099987)
4. Clappers N, Brouwer MA, Verheugt FW. Antiplatelet treatment for coronary heart disease. Heart 2007;93:258-265. (Pubitemid 46180312)
5. Colman RW. ADP receptors in platelets. Ann N Y Acad Sci 1990;603:198-209; discussion 110.
6. O'Brien JR, Heywood JB. Effect of aggregating agents and their inhibitors on the mean platelet shape. J Clin Pathol 1966;19:148-153.
7. Born GV. Observations on the change in shape of blood platelets brought about by adenosine diphosphate. J Physiol 1970;209:487-511.
8. Kidane AG, Salacinski H, Tiwari A, et al. Anticoagulant and antiplatelet agents: Their clinical and device application(s) together with usages to engineer surfaces. Biomacromolecules 2004;5:798-813. (Pubitemid 38702248)
9. Gonzalez ER. Antiplatelet therapy in atherosclerotic cardiovascular disease. Clin Ther 1998;20(Suppl B):B18-B41. (Pubitemid 128646607)
10. Lablanche JM, McFadden EP, Bonnet JL, et al. Combined antiplatelet therapy with ticlopidine and aspirin. A simplified approach to intracoronary stent management. Eur Heart J 1996;17:1373-1380.
11. Depta JP, Bhatt DL. Aspirin and platelet adenosine diphosphate receptor antagonists in acute coronary syndromes and percutaneous coronary intervention: Role in therapy and strategies to overcome resistance. Am J Cardiovasc Drugs 2008;8:91-112.
12. Goods CM, al-Shaibi KF, Liu MW, et al. Comparison of aspirin alone versus aspirin plus ticlopidine after coronary artery stenting. Am J Cardiol 1996;78:1042-1044.
13. Keighley CS, Urban P, Killer II, et al. Palmaz-Schatz coronary stent implantation without intravascular ultrasound and without subsequent anticoagulation: Clinical outcome. J Invasive Cardiol 1996;8:185-190. (Pubitemid 126736631)
14. Park SW, Park SJ, Hong MK, et al. Coronary stenting (Cordis) without anticoagulation. Am J Cardiol 1997;79:901-904.
15. Schatz RA, Baim DS, Leon M, et al. Clinical experience with the Palmaz-Schatz coronary stent. Initial results of a multicenter study. Circulation 1991;83:148-161.
16. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: Observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation 2003;108:1682-1687.
17. DiPerri T, Pasini FL, Frigerio C, et al. Pharmacodynamics of ticlopidine in man in relation to plasma and blood cell concentration. Eur J Clin Pharmacol 1991;41:429-434.
18. Weber AA, Braun M, Hohlfeld T, et al. Recovery of platelet function after discontinuation of clopidogrel treatment in healthy volunteers. Br J Clin Pharmacol 2001;52:333-336. (Pubitemid 33796233)
19. Di Minno G, Cerbone AM, Mattioli PL, et al. Functionally thrombasthenic state in normal platelets following the administration of ticlopidine. J Clin Invest 1985;75:328-338. (Pubitemid 15143470)
20. Gent M, Blakely JA, Easton JD, et al. The Canadian American Ticlopidine Study (CATS) in thromboembolic stroke. Lancet 1989;1:1215-1220. (Pubitemid 19140324)
21. Puri RN, Colman RW. ADP-induced platelet activation. Crit Rev Biochem Mol Biol 1997;32:437-502.
22. Saltiel E, Ward A. Ticlopidine. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy in platelet-dependent disease states. Drugs 1987;34:222-262. (Pubitemid 17092322)
23. Jacobson AK. Platelet ADP receptor antagonists: ticlopidine and clopidogrel. Best Pract Res Clin Haematol 2004;17:55-64.
24. Albers GW, Amarenco P, Easton JD, et al Antithrombotic and thrombolytic therapy for ischemic stroke: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):630S-669S. (Pubitemid 351892974)
25. Crawford KM, Talbert RL. Antiplatelet therapy in secondary stroke prevention. Expert Opin Pharmacother 2001;2:1609-1613. (Pubitemid 33019729)
26. Fleck JD, Biller J. Choices in medical management for prevention of acute ischemic stroke. Curr Neurol Neurosci Rep 2001;1:33-38.
27. Hass WK, Easton JD, Adams HP Jr, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989;321:501-507.
28. Ito E, Takahashi A, Yamamoto H, et al. Ticlopidine alone versus ticlopidine plus aspirin for preventing recurrent stroke. Intern Med 2003;42:793-799. (Pubitemid 37258691)
29. Ito MK, Smith AR, Lee ML. Ticlopidine: A new platelet aggregation inhibitor. Clin Pharm 1992;11:603-617.
30. Hass WK, Easton JD, Adams HP Jr, et al. A randomized trial comparing ticlopidine hydrochloride with aspirin for the prevention of stroke in high-risk patients. Ticlopidine Aspirin Stroke Study Group. N Engl J Med 1989;321:501-507.
31. Lubbe DF, Berger PB. The thienopyridines. J Interv Cardiol 2002;15:85-93.
32. Bhatt DL, Bertrand ME, Berger PB, et al. Meta-analysis of randomized and registry comparisons of ticlopidine with clopidogrel after stenting. J Am Coll Cardiol 2002;39:9-14.
33. Ono K, Kurohara K, Yoshihara M, et al. Agranulocytosis caused by ticlopidine and its mechanism. Am J Hematol 1991;37:239-242.
34. Muszkat M, Shapira MY, Sviri S, et al. Ticlopidine-induced thrombotic thrombocytopenic purpura. Pharmacotherapy 1998;18:1352-1355.
35. Steinhubl SR, Tan WA, Foody JM, Topol EJ. Incidence and clinical course of thrombotic thrombocytopenic purpura due to ticlopidine following coronary stenting. EPISTENT Investigators. Evaluation of platelet IIb/IIIa inhibitor for stenting. JAMA 1999;281:806-810.
36. Mataix R, Ojeda E, Perez MC, Jimenez S. Ticlopidine and severe aplastic anaemia. Br J Haematol 1992;80:125-126.
37. Ferrer F, De Arriba F, Moraleda JM, Vicente V. Aplastic anemia induced by ticlopidine after placement of coronary artery stents: Therapeutic role of granulocyte colony stimulating factor. Clin Drug Investig 1998;15:261-262. (Pubitemid 28163753)
38. Prescribing information: Ticlid (ticlopidine hydrochloride) tablets. In: Physicians Desk Reference.Montvale, New Jersey: Medical Economics Co., 2004.
39. McTavish D, Faulds D, Goa KL. Ticlopidine. An updated review of its pharmacology and therapeutic use in platelet-dependent disorders. Drugs 1990;40:238-259. Medical Economics Co., 2004. (Pubitemid 120032421)
40. Desager JP. Clinical pharmacokinetics of ticlopidine. Clin Pharmacokinet 1994;26:347-355.
41. Knudsen JB, Bastain W, Sefton CM, et al. Pharmacokinetics of ticlopidine during chronic oral administration to healthy volunteers and its effects on antipyrine pharmacokinetics. Xenobiotica 1992;22:579-589.
42. Picard-Fraire C. Ticlopidine hydrochloride: Relationship between dose, kinetics, plasma concentration and effect on platelet function. Thromb Res Suppl 1983;4:119-128.
43. Enjalbert R, Galy J. Structure of ticlopidine hydrochloride - A platelet antiaggregating agent. Acta Cryst 1992;48:1043-1045.
44. Dalvie DK, O'Connell TN. Characterization of novel dihydrothienopyridinium and thienopyridinium metabolites of ticlopidine in vitro: Role of peroxidases, cytochromes p450, and monoamine oxidases. Drug Metab Dispos 2004;32:49-57.
45. Yoneda K, Iwamura R, Kishi H, et al. Identification of the active metabolite of ticlopidine from rat in vitro metabolites. Br J Pharmacol 2004;142:551-557. (Pubitemid 38869869)
46. Ha-Duong NT, Dijols S, Macherey A, et al. Ticlopidine as a selective mechanism-based inhibitor of human cytochrome P450 2C19. Biochemistry 2001;40:12112-12122. (Pubitemid 32946552)
47. Richter T, Murdter TE, Heinkele G, et al. Potent mechanism-based inhibition of human CYP2B6 by clopidogrel and ticlopidine. J Pharmacol Exp Ther 2004;308:189-197. (Pubitemid 38090717)
48. Zhan C, Yang J, Dong XC, Wang YL. Molecular modeling of purinergic receptor P2Y12 and interaction with its antagonists. J Mol Graph Model 2007;26:20-31. (Pubitemid 46977248)
49. Mills DC. ADP receptors on platelets. Thromb Haemost 1996;76:835-856.
50. Jantzen HM, Gousset L, Bhaskar V, et al. Evidence for two distinct G-protein-coupled ADP receptors mediating platelet activation. Thromb Haemost 1999;81:111-117. (Pubitemid 29041659)
51. Kunapuli SP. Multiple P2 receptor subtypes on platelets: A new interpretation of their function. Trends Pharmacol Sci 1998;19:391-394.
52. Fabre JE, Nguyen M, Latour A, et al. Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice. Nat Med 1999;5:1199-1202. (Pubitemid 29474427)
53. 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;107:1591-1598.
54. Zhang FL, Luo L, Gustafson E, et al. ADP is the cognate ligand for the orphan G protein-coupled receptor SP1999. J Biol Chem 2001;276:8608-8615. (Pubitemid 37385678)
55. Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001;409:202-207. (Pubitemid 32144286)
56. Ayyanathan K, Webbs TE, Sandhu AK, et al. Cloning and chromosomal localization of the human P2Y1 purinoceptor. Biochem Biophys Res Commun 1996;218:783-788. (Pubitemid 26050740)
57. Hechler B, Leon C, Vial C, et al. The P2Y1 receptor is necessary for adenosine 5′-diphosphate-induced platelet aggregation. Blood 1998;92:152-159. (Pubitemid 28303187)
58. Hechler B, Cattaneo M, Gachet C. The P2 receptors in platelet function. Semin Thromb Hemost 2005;31:150-161.
59. Bennett JS. Novel platelet inhibitors. Annu Rev Med 2001;52:161-184.
60. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000;84:891-896. (Pubitemid 30946954)
61. Leon C, Vial C, Gachet C, et al. The P2Y1 receptor is normal in a patient presenting a severe deficiency of ADP-induced platelet aggregation. Thromb Haemost 1999;81:775-781.
62. Humphries RG, Robertson MJ, Leff P. A novel series of P2T purinoceptor antagonists: Definition of the role of ADP in arterial thrombosis. Trends Pharmacol Sci 1995;16:179-181.
63. Cattaneo M, Gachet C. ADP receptors and clinical bleeding disorders. Arterioscler Thromb Vasc Biol 1999;19:2281-2285. (Pubitemid 29477827)
64. Baurand A, Eckly A, Bari N, et al. Desensitization of the platelet aggregation response to ADP: differential down-regulation of the P2Y1 and P2cyc receptors. Thromb Haemost 2000;84:484-491. (Pubitemid 30702250)
65. Ding Z, Kim S, Dorsam RT, et al. Inactivation of the human P2Y12 receptor by thiol reagents requires interaction with both extracellular cysteine residues, Cys17 and Cys270. Blood 2003;101:3908-3914. (Pubitemid 36857866)
66. Hoffmann C, Moro S, Nicholas RA, et al. The role of amino acids in extracellular loops of the human P2Y1 receptor in surface expression and activation processes. J Biol Chem 1999;274:14639-14647. (Pubitemid 129518788)
67. Savi P, Zachayus JL, Delesque-Touchard N, et al. The active metabolite of clopidogrel disrupts P2Y12 receptor oligomers and partitions them out of lipid rafts. Proc Natl Acad Sci USA 2006;103:11069-11074. (Pubitemid 44148419)
68. Bhatt DL, Scheiman J, Abraham NS, et al. 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. Circulation 2008;18:1894-1909.
69. Hankey GJ, Sudlow CL, Dunbabin DW. Thienopyridine derivatives (ticlopidine, clopidogrel) versus aspirin for preventing stroke and other serious vascular events in high vascular risk patients. Cochrane Database Syst Rev 2000, CD001246.
70. Jarvis B, Simpson K. Clopidogrel: A review of its use in the prevention of atherothrombosis. Drugs 2000;60:347-377. (Pubitemid 30680398)
71. Feliste R, Delebassee D, Simon MF, et al. Broad spectrum anti-platelet activity of ticlopidine and PCR 4099 involves the suppression of the effects of released ADP. Thromb Res 1987;48:403-415. (Pubitemid 18127022)
72. CAPRIE Steering Committee. A randomized, blinded trial of SR25990C versus aspirin in patients at risk of ischemic events (CAPRIE). Lancet 1996;348:1329-1339.
73. Verstraete M, Zoldhelyi P. Novel antithrombotic drugs in development. Drugs 1995;49:856-884.
74. Yusuf S, Zhao F, Mehta SR, et al. 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. (Pubitemid 32758501)
75. Patrono C, Bachmann F, Baigent C, et al. Expert consensus document on the use of antiplatelet agents. The task force on the use of antiplatelet agents in patients with atherosclerotic cardiovascular disease of the European society of cardiology. Eur Heart J 2004;25:166-181. (Pubitemid 38112156)
76. Thebault JJ, Kieffer G, Lowe GD, et al. Repeated-dose pharmacodynamics of clopidogrel in healthy subjects. Semin Thromb Hemost 1999;25(Suppl 2):9-14. (Pubitemid 29350285)
77. Pedersen AK, FitzGerald GA. Dose-related kinetics of aspirin. Presystemic acetylation of platelet cyclooxygenase. N Engl J Med 1984;311:1206-1211.
78. Gurbel PA, Bliden KP, Hiatt BL, O'Connor CM. Clopidogrel for coronary stenting: Response variability, drug resistance, and the effect of pretreatment platelet reactivity. Circulation 2003;107:2908-2913.
79. Muller I, Besta F, Schulz C, et al. Prevalence of clopidogrel non-responders among patients with stable angina pectoris scheduled for elective coronary stent placement. Thromb Haemost 2003;89:783-787. (Pubitemid 36603418)
80. 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.
81. Vats HS, Hocking WG, Rezkalla SH. Suspected clopidogrel resistance in a patient with acute stent thrombosis. Nat Clin Pract Cardiovasc Med 2006;3:226-230; Quiz 232.
82. Gurbel PA, Lau WC, Bliden KP, Tantry US. Clopidogrel resistance: Implications for coronary stenting. Curr Pharm Des 2006;12:1261-1269.
83. De Miguel A, Ibanez B, Badimon JJ. Clinical implications of clopidogrel resistance. Thromb Haemost 2008;100:196-203.
84. Celik T, Iyisoy A, Gul H, Isik E. Clopidogrel resistance: A diagnostic challenge. Int J Cardiol 2009;131:267-268; Author Reply 268-269.
85. Harrison P, Frelinger AL 3rd, Furman MI, Michelson AD. Measuring antiplatelet drug effects in the laboratory. Thromb Res 2007;120:323-336.
86. Wiviott SD, Antman EM. Clopidogrel resistance: A new chapter in a fast-moving story. Circulation 2004;109:3064-3067.
87. Jaremo P, Lindahl TL, Fransson SG, Richter A. Individual variations of platelet inhibition after loading doses of clopidogrel. J Intern Med 2002;252:233-238.
88. Saw J, Steinhubl SR, Berger PB, et al. Lack of adverse clopidogrel-atorvastatin clinical interaction from secondary analysis of a randomized, placebo-controlled clopidogrel trial. Circulation 2003;108:921-924. (Pubitemid 37048218)
89. Frere C, Cuisset T, Morange PE, et al. Effect of cytochrome p450 polymorphisms on platelet reactivity after treatment with clopidogrel in acute coronary syndrome. Am J Cardiol 2008;101:1088-1093.
90. Lau WC, Gurbel PA, Watkins PB, et al. Contribution of hepatic cytochrome P450 3A4 metabolic activity to the phenomenon of clopidogrel resistance. Circulation 2004;109:166-171.
91. Savi P, Combalbert J, Gaich C, et al. The antiaggregating activity of clopidogrel is due to a metabolic activation by hepatic cytochrome P450-1A. Thrombos Haemost 1994;72:313-317. (Pubitemid 24251300)
92. Meunier B, de Visser SP, Shaik S. Mechanism of oxidation reactions catalyzed by cytochrome p450 enzymes. Chem Rev 2004;104:3947-3980.
93. Clarke TA, Waskell LA. The metabolism of clopidogrel is catalyzed by human cytochrome P450 3A and is inhibited by atorvastatin. Drug Metab Dispos 2003;31:53-59. (Pubitemid 36735258)
94. Savi P, Pereillo JM, Uzabiaga MF, et al. Identification and biological activity of the active metabolite of clopidogrel. Thromb Haemost 2000;84:891-896. (Pubitemid 30946954)
95. Nguyen TA, Diodati JG, Pharand C. Resistance to clopidogrel: A review of the evidence. J Am Coll Cardiol 2005;45:1157-1164.
96. Geiger J, Honig-Lied P, Schanzenbacher P, Walter U. Ligand specificity and ticlopidine effects distinguish three platelet ADP receptors. Eur J Pharmacol 1998;351:235-246. (Pubitemid 28312936)
97. Schroer K. Antiplatelet drugs: A comprehensive review. Drugs 1995;50:7-28.
98. Jin J, Kunapuli SP. Activation of two different G protein-coupled receptors is essential for ADP-induced platelet aggregation. Proc Natl Acad Sci USA 1998;95:8070-8074. (Pubitemid 28326067)
99. Hollopeter G, Jantzen HM, Vincent D, et al. Identification of the platelet ADP receptor targeted by antithrombotic drugs. Nature 2001;409:202-207. (Pubitemid 32144286)
100. Barone-Rochette G, Ormezzano O, Polack B, et al. Resistance to platelet antiaggregants: An important cause of very late thrombosis of drug eluting stents? Observations from five cases. Arch Cardiovasc Dis 2008;101:100-107.
101. Bonello L, Paganelli F, Arpin-Bornet M, et al. Vasodilator-stimulated phosphoprotein phosphorylation analysis prior to percutaneous coronary intervention for exclusion of postprocedural major adverse cardiovascular events. J Thromb Haemost 2007;5:1630-1636. (Pubitemid 47091403)
102. Hezard N, Metz D, Garnotel R, et al. Platelet VASP phosphorylation assessment in clopidogrel-treated patients: Lack of agreement between Western blot and flow cytometry. Platelets 2005;16:474-481. (Pubitemid 43109921)
103. Blindt R, Stellbrink K, de Taeye A, et al. The significance of vasodilator-stimulated phosphoprotein for risk stratification of stent thrombosis. Thromb Haemost 2007;98:1329-1334. (Pubitemid 350239106)
104. Niitsu Y, Sugidachi A, Ogawa T, et al. Repeat oral dosing of prasugrel, a novel P2Y(12) receptor inhibitor, results in cumulative and potent antiplatelet and antithrombotic activity in several animal species. Eur J Pharmacol 2008;579:276-282.
105. 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;129:1439-1446. (Pubitemid 30175717)
106. 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;27:1166-1173. (Pubitemid 43752387)
107. 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-e16.
108. Jakubowski JA, Payne CD, Weerakkody GJ, et al. Dose-dependent inhibition of human platelet aggregation by prasugrel and its interaction with aspirin in healthy subjects. J Cardiovasc Pharmacol 2007;49:167-173.
109. Hagihara K, Kurihara A, Kawai K, et al. Absorption, distribution and excretion of the new thienopyridine agent prasugrel in rats. Xenobiotica 2007;37:788-801. (Pubitemid 47057126)
110. Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos 2007;35:1096-1104.
111. Wiviott SD, Trenk D, Frelinger AL, et al. Prasugrel compared with high loading- and maintenance-dose clopidogrel in patients with planned percutaneous coronary intervention: The Prasugrel in Comparison to Clopidogrel for Inhibition of Platelet Activation and Aggregation-Thrombolysis in Myocardial Infarction 44 trial. Circulation 2007;116:2923-2932. (Pubitemid 350291199)
112. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015. (Pubitemid 350106708)
113. Wiviott SD, Braunwald E, McCabe CH, et al; for the TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007;357:2001-2015.
114. 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;81:735-741.
115. 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;34:600-607.