Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy chinese and white volunteers: An open-label trial

Clinical Therapeutics

Volumn 32, Issue 2, 2010, Pages 365-379

  Small, David S ^a   Payne, Christopher D ^a   Kothare, Prajakti ^a   Yuen, Eunice ^a   Natanegara, Fanni ^a   Teng Loh, Mei ^b   Jakubowski, Joseph A ^a   Richard Lachno, D ^a   Li, Ying G ^a   Winters, Kenneth J ^a   Farid, Nagy A ^a   Ni, Lan ^a   Salazar, Daniel E ^c   Tomlin, Molly ^a   Kelly, Ronan ^b  

^a ELI LILLY AND COMPANY   (United States)

^b NATIONAL UNIVERSITY OF SINGAPORE   (Singapore)

^c DAIICHI SANKYO INC   (United States)

Author keywords

clopidogrel; East Asian population; platelet aggregation; prasugrel

Indexed keywords

CLOPIDOGREL; DRUG METABOLITE; PRASUGREL; VASODILATOR STIMULATED PHOSPHOPROTEIN;

ADULT; AREA UNDER THE CURVE; ARTICLE; BLEEDING; BLOOD SAMPLING; BODY WEIGHT; CAUCASIAN; CHINESE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; CONTUSION; CROSSOVER PROCEDURE; DRUG BLOOD LEVEL; DRUG RESPONSE; DRUG TOLERABILITY; EPISTAXIS; FEMALE; FLOW CYTOMETRY; HEMOPTYSIS; HUMAN; LIQUID CHROMATOGRAPHY; LOADING DRUG DOSE; MALE; MASS SPECTROMETRY; MAXIMUM PLASMA CONCENTRATION; OPEN STUDY; RANDOMIZED CONTROLLED TRIAL; RECTUM HEMORRHAGE; SINGAPORE; SINGLE DRUG DOSE; THROMBOCYTE AGGREGATION INHIBITION; TIME TO MAXIMUM PLASMA CONCENTRATION;

ADMINISTRATION, ORAL; ADULT; ASIAN CONTINENTAL ANCESTRY GROUP; BLOOD PLATELETS; CELL ADHESION MOLECULES; CHINA; EUROPEAN CONTINENTAL ANCESTRY GROUP; FEMALE; FLOW CYTOMETRY; HUMANS; MALE; MICROFILAMENT PROTEINS; MIDDLE AGED; PHOSPHOPROTEINS; PIPERAZINES; PLATELET AGGREGATION; PLATELET AGGREGATION INHIBITORS; PLATELET FUNCTION TESTS; RECEPTORS, PURINERGIC P2; SINGAPORE; THIOPHENES; TICLOPIDINE; YOUNG ADULT;

EID: 77649332028     PISSN: 01492918     EISSN: 1879114X     Source Type: Journal    
DOI: 10.1016/j.clinthera.2010.02.015     Document Type: Article

References (21)

1. Gachet C. Regulation of platelet functions by P2 receptors. Annu Rev Pharmacol Toxicol. 46 (2006) 277-300
2. electronic Medicines Compendium. Summary of product characteristics. Efient 5mg & 10mg film-coated tablets (Eli Lilly and Company Limited/Daiichi Sankyo UK Limited). http://emc.medicines.org.uk/medicine/21504/SPC/Efient+5mg+%26+10mg+film- coated+tablets+(Eli+Lilly+and+Company+Ltd+Daiichi+Sankyo+UK+Limited)/#ix zz0MZgmdJ5u Accessed July 28, 2009
3. Ernest II C.S., Small D.S., Rohatagi S., et al. Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease. J Pharmacokinet Pharmacodyn. 35 (2008) 593-618
4. Jakubowski J.A., Winters K.J., Naganuma H., and Wallentin L. A review of preclinical and clinical studies and the mechanistic basis for its distinct antiplatelet profile. Cardiovasc Drug Rev. 25 (2007) 357-374
5. 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. 153 66 (2007) e9-e16
6. 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 aspirintreated patients with stable coronary artery disease. Eur Heart J. 27 (2006) 1166-1173
7. Wiviott S.D., Trenk D., Frelinger A.L., et al., PRINCIPLE-TIMI 44 Investigators. Prasugrel compared with high loading- and maintenancedose 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. 116 (2007) 2923-2932
8. Wiviott S.D., Braunwald E., McCabe C.H., et al., TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 357 (2007) 2001-2015
9. Small D.S., Kothare P., Yuen E., et al. The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects. Eur J Clin Pharmacol. 66 (2010) 127-135
10. Jakubowski J.A., Payne C.D., Li Y.G., et al. A comparison of the antiplatelet effects of prasugrel and high-dose clopidogrel as assessed by VASP-phosphorylation and light transmission aggregometry. Thromb Haemost. 99 (2008) 215-222
11. Jakubowski J.A., Payne C.D., Li Y.G., et al. The use ofthe Verify Now P2Y12 point-of-care device to monitor platelet function across a range of P2Y12 inhibition levels following prasugrel and clopidogrel administration. Thromb Haemost. 99 (2008) 409-415
12. Jakubowski J.A., Payne C.D., Weerakkody G.J., et al. Dose-dependent inhibition of human platelet aggregation by prasugrel and its interaction with aspirin in healthy subjects. J Cardiovasc Pharmacol. 49 (2007) 167-173
13. Farid N.A., Small D.S., Payne C.D., et al. Effect of atorvastatin on the pharmacokinetics and pharmaco-dynamics of prasugrel and clopidogrel in healthy subjects. Pharmacotherapy. 28 (2008) 1483-1494
14. Small D.S., Farid N.A., Payne C.D., et al. Effects of the proton pump inhibitor lansoprazole on the pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel. J Clin Pharmacol. 48 (2008) 475-484
15. Small D.S., Wrishko R.E., Ernest II C.S., et al. Effect of age on the pharma-cokinetics and pharmacodynamics of prasugrel during multiple dosing: An open-label, single-sequence, clinical trial. Drugs Aging. 26 (2009) 781-790
16. Small D., Wrishko R., Ernest II C.S., et al. Comparison of the pharmacokinetics and pharmacodynamics of prasugrel in subjects with end-stage renal disease and healthy subjects. Presented at: Ninth World Conference on Clinical Pharmacology and Therapeutics. Quebec, Canada (July 27-August 1, 2008)
17. Wallentin L., Varenhorst C., James S., et al. Prasugrel achieves greater and faster P2Y12 receptor-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. 29 (2008) 21-30
18. Farid N.A., 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. 21 (2007) 169-179
19. Takahashi M., Pang H., Kawabata K., et al. Quantitative determination of clopidogrel active metabolite in human plasma by LC-MS/MS. J Pharm Biomed Anal. 48 (2008) 1219-1224
20. Salazar D.E., Ernest II C.S., Wrishko R.E., et al. Relationship between exposure to the prasugrel active metabolite with TIMI major/minor bleeding in TRITON-TIMI 38. Circulation 118 Suppl 2 (2008) S815 Abstract 4001
21. ClinicalTrials.gov. A comparison of antiplatelet therapies in Asian subjects with acute coronary syndrome. http://www.clinicaltrials.gov/ct2/show/NCT00830960?term=A+Comparison+of+ Antiplatelet+Therapies+in+Asian+Subjects+With+Acute+Coronary+ Syndrome&rank=1 Accessed April 17, 2009