The active metabolite of prasugrel inhibits adenosine diphosphate- and collagen-stimulated platelet procoagulant activities

Journal of Thrombosis and Haemostasis

Volumn 6, Issue 2, 2008, Pages 359-365

  Frelinger, A L ^a   Jakubowski, J A ^a   Li, Y ^a   Barnard, M R ^a   Linden, M D ^a   Tarnow, I ^a,c   Fox, M L ^a   Sugidachi, A ^d   Winters, K J ^b   Furman, M I ^b   Michelson, A D ^a  

^a UNIVERSITY OF MASSACHUSETTS MEDICAL SCHOOL   (United States)

^b ELI LILLY AND COMPANY   (United States)

^c UNIVERSITY OF COPENHAGEN   (Denmark)

^d DAIICHI SANKYO CO   (Japan)

Author keywords

Antiplatelet; Phosphatidylserine; Platelets; Prasugrel; Thienopyridine; Thrombin; Tissue factor

Indexed keywords

ADENOSINE DIPHOSPHATE; ANTITHROMBOCYTIC AGENT; COLLAGEN; DRUG METABOLITE; LIPOCORTIN 5; PHOSPHATIDYLCHOLINE; PHOSPHATIDYLSERINE; PRASUGREL; PURINERGIC P2Y12 RECEPTOR; R 138727; THROMBIN; THROMBOPLASTIN; UNCLASSIFIED DRUG;

ANTICOAGULATION; ARTICLE; BLOOD CLOTTING; BLOOD FLOW; CELL AGGREGATION; CELL STIMULATION; CELL SURFACE; CONTROLLED STUDY; CYTOMETRY; DRUG ACTIVITY; HUMAN; HUMAN CELL; IC 50; MONOCYTE; PRIORITY JOURNAL; PROTEIN EXPRESSION; THROMBOCYTE; THROMBOCYTE AGGREGATION INHIBITION; THROMBOELASTOGRAPHY;

ADENOSINE DIPHOSPHATE; ANNEXIN A5; BIOTRANSFORMATION; BLOOD COAGULATION FACTORS; BLOOD PLATELETS; CLOT RETRACTION; COLLAGEN; HUMANS; MONOCYTES; PHOSPHATIDYLSERINES; PIPERAZINES; PLATELET ACTIVATION; PRODRUGS; RECEPTORS, PURINERGIC P2; THIOPHENES; THROMBELASTOGRAPHY; THROMBIN; THROMBOPLASTIN;

EID: 38349140973     PISSN: 15387933     EISSN: 15387836     Source Type: Journal    
DOI: 10.1111/j.1538-7836.2007.02838.x     Document Type: Article

References (36)

1. 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.
2. Cattaneo M. ADP receptor antagonists. In: Michelson AD, ed. Platelets, 2nd edn. San Diego: Elsevier/Academic Press, 2007: 201-20.
3. Sugidachi A, Ogawa T, Kurihara A, Hagihara K, Jakubowski JA, Hashimoto M, Niitsu Y, Asai F. The greater in vivo antiplatelet effects of prasugrel compared to clopidogrel reflect more efficient generation of its active metabolite with similar antiplatelet activity to clopidogrel's active metabolite. J Thromb Haemost. 2007; 5: 1545-51.
4. Matsushima N, Jakubowski JA, Asai F, Naganuma H, Brandt JT, Hirota T, Freestone S, Winters KJ. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: A multiple-dose study in healthy humans. Platelets 2006; 17: 218-26.
5. Jakubowski JA, Payne CD, Brandt JT, Weerakkody GJ, Farid NA, Small DS, Naganuma H, Li GY, Winters KJ. 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.
6. Asai F, Jakubowski JA, Naganuma H, Brandt JT, Matsushima N, Hirota T, Freestone S, Winters KJ. Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: A single ascending dose study in healthy humans. Platelets 2006; 17: 209-17.
7. Jakubowski JA, Matsushima N, Asai F, Naganuma H, Brandt JT, Hirota T, Freestone S, Winters KJ. 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: 421-30.
8. Bouchard BA, Butenas S, Mann KG, Tracy PB. Interactions between platelets and the coagulation system. In: Michelson AD, ed. Platelets, 2nd edn. San Diego: Elsevier, 2007: 377-402.
9. Storey RF, Sanderson HM, White AE, May JA, Cameron KE, Heptinstall S. The central role of the P(2T) receptor in amplification of human platelet activation, aggregation, secretion and procoagulant activity. Br J Haematol 2000; 110: 925-34.
10. Atkinson BT, Jarvis GE, Watson SP. Activation of GPVI by collagen is regulated by alpha2beta1 and secondary mediators. J Thromb Haemost 2003; 1: 1278-87.
11. Dorsam RT, Tuluc M, Kunapuli SP. Role of protease-activated and ADP receptor subtypes in thrombin generation on human platelets. J Thromb Haemost 2004; 2: 804-12.
12. Hasegawa M, Sugidachi A, Ogawa T, Isobe T, Jakubowski JA, Asai F. 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.
13. Jernberg T, Payne CD, Winters KJ, Darstein C, Brandt JT, Jakubowski JA, Naganuma H, Siegbahn A, Wallentin L. 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.
14. Morrissey JH, Agis H, Albrecht S. CD142 (tissue factor) Workshop Panel report. In: Kishimoto T, Kikutani H, von dem Borne A, et al., eds. Leucocyte Typing VI: White Cell Differentiation Antigens. New York: Garland Publishing, Inc., 1997: 742-6.
15. Muller M, Albrecht S, Golfert F, Hofer A, Funk RH, Magdolen V, Flossel C, Luther T. Localization of tissue factor in actin-filament-rich membrane areas of epithelial cells. Exp Cell Res 1999; 248: 136-47.
16. Michelson AD, Linden MD, Barnard MR, Furman MI, Frelinger AL III. Flow cytometry. In: Michelson AD, ed. Platelets, 2nd edn. San Diego: Elsevier/ Academic Press, 2007: 545-63.
17. Barnard MR, Linden MD, Frelinger AL III, Li Y, Fox ML, Furman MI, Michelson AD. Effects of platelet binding on whole blood flow cytometry assays of monocyte and neutrophil procoagulant activity. J Thromb Haemost 2005; 3: 2563-70.
18. Hobson AR, Agarwala RA, Swallow RA, Dawkins KD, Curzen NP. Thrombelastography: Current clinical applications and its potential role in interventional cardiology. Platelets 2006; 17: 509-18.
19. Salooja N, Perry DJ. Thrombelastography. Blood Coagul Fibrinolysis 2001; 12: 327-37.
20. Berkowitz SD, Frelinger AL III, Hillman RS. Progress in point-of-care laboratory testing for assessing platelet function. Am Heart J 1998; 136: S51-65.
21. Michelson AD, Rajasekhar D, Bednarek FJ, Barnard MR. Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: Differences between neonates and adults. Thromb Haemost 2000; 84: 689-94.
22. Furman MI, Krueger LA, Frelinger AL III, Barnard MR, Mascelli MA, Nakada MT, Michelson AD. GPIIb-IIIa antagonist-induced reduction in platelet surface factor V/Va binding and phosphatidylserine expression in whole blood. Thromb Haemost 2000; 84: 492-8.
23. Zhao L, Bath PM, May J, Losche W, Heptinstall S. P-selectin, tissue factor and CD40 ligand expression on platelet-leucocyte conjugates in the presence of a GPIIb/IIIa antagonist. Platelets 2003; 14: 473-80.
24. Zillmann A, Luther T, Muller I, Kotzsch M, Spannagl M, Kauke T, Oelschlagel U, Zahler S, Engelmann B. Platelet-associated tissue factor contributes to the collagen-triggered activation of blood coagulation. Biochem Biophys Res Commun 2001; 281: 603-9.
25. Muller I, Klocke A, Alex M, Kotzsch M, Luther T, Morgenstern E, Zieseniss S, Zahler S, Preissner K, Engelmann B. Intravascular tissue factor initiates coagulation via circulating microvesicles and platelets. FASEB J 2003; 17: 476-8.
26. Siddiqui FA, Desai H, Amirkhosravi A, Amaya M, Francis JL. The presence and release of tissue factor from human platelets. Platelets 2002; 13: 247-53.
27. Leon C, Ravanat C, Freund M, Cazenave JP, Gachet C. Differential involvement of the P2Y1 and P2Y12 receptors in platelet procoagulant activity. Arterioscler Thromb Vasc Biol 2003; 23: 1941-7.
28. van der Meijden PE, Feijge MA, Giesen PL, Huijberts M, van Raak LP, Heemskerk JW. Platelet P2Y12 receptors enhance signalling towards procoagulant activity and thrombin generation. A study with healthy subjects and patients at thrombotic risk. Thromb Haemost 2005; 93: 1128-36.
29. Pereillo JM, Maftouh M, Andrieu A, Uzabiaga MF, Fedeli O, Savi P, Pascal M, Herbert JM, Maffrand JP, Picard C. Structure and stereochemistry of the active metabolite of clopidogrel. Drug Metab Dispos 2002; 30: 1288-95.
30. Taubert D, Kastrati A, Harlfinger S, Gorchakova O, Lazar A, von Beckerath N, Schomig A, Schomig E. Pharmacokinetics of clopidogrel after administration of a high loading dose. Thromb Haemost 2004; 92: 311-6.
31. Frelinger AL III, Jakubowski JA, Li Y, Barnard MR, Fox ML, Linden MD, Sugidachi A, Winters KJ, Furman MI, Michelson AD. The active metabolite of prasugrel inhibits ADP-stimulated thrombo-inflammatory markers of platelet activation: Influence of other blood cells, calcium, and aspirin. Thromb Haemost 2007; 98: 192-200.
32. Behan MW, Fox SC, Heptinstall S, Storey RF. Inhibitory effects of P2Y12 receptor antagonists on TRAP-induced platelet aggregation, procoagulant activity, microparticle formation and intracellular calcium responses in patients with acute coronary syndromes. Platelets 2005; 16: 73-80.
33. Linden MD, Frelinger AL III, Barnard M, Furman MI, Michelson AD. A novel mechanism of action of clopidogrel: Inhibition of monocyte procoagulant activity. J Thromb Haemost 2005; 3: P0357.
34. Leon C, Alex M, Klocke A, Morgenstern E, Moosbauer C, Eckly A, Spannagl M, Gachet C, Engelmann B. Platelet ADP receptors contribute to the initiation of intravascular coagulation. Blood 2004; 103: 594-600.
35. Gurbel PA, Bliden KP, Guyer K, Aggarwal N, Tantry US. Delayed thrombin-induced platelet-fibrin clot generation by clopidogrel: A new dose-related effect demonstrated by thrombelastography in patients undergoing coronary artery stenting. Thromb Res 2007; 119: 563-70.
36. Evangelista V, Manarini S, Dell'Elba G, Martelli N, Napoleone E, Di Santo A, Lorenzet PS. Clopidogrel inhibits platelet-leukocyte adhesion and platelet-dependent leukocyte activation. Thromb Haemost 2005; 94: 568-77.