Prediction of prasugrel active metabolite concentrations from 2 downstream inactive metabolite concentrations using multilinear regression analysis

Journal of Clinical Pharmacology

Volumn 49, Issue 8, 2009, Pages 973-983

  Ernest, C Steven ^a   Heathman, Michael A ^a   Wrishko, Rebecca E ^a  

^a ELI LILLY AND COMPANY   (United States)

Author keywords

Model; Pharmacokinetics; Prasugrel; Prediction of active metabolite

Indexed keywords

DRUG METABOLITE; KETOCONAZOLE; PRASUGREL; R 106583; R 119251; UNCLASSIFIED DRUG;

ADULT; AGED; ARTICLE; CLINICAL ARTICLE; CORRELATION ANALYSIS; CREATININE CLEARANCE; DRUG DISTRIBUTION; ETHNICITY; FEMALE; HUMAN; LINEAR REGRESSION ANALYSIS; LIVER FAILURE; LOADING DRUG DOSE; MALE; PLASMA CONCENTRATION-TIME CURVE; PREDICTION; QUANTITATIVE ANALYSIS; SMOKING;

ADOLESCENT; ADULT; AGED; CLINICAL TRIALS, PHASE III AS TOPIC; DOSE-RESPONSE RELATIONSHIP, DRUG; FEMALE; HUMANS; LINEAR MODELS; MALE; MIDDLE AGED; MODELS, BIOLOGICAL; PIPERAZINES; PLATELET AGGREGATION INHIBITORS; PRODRUGS; THIOPHENES; YOUNG ADULT;

EID: 70349269874     PISSN: 00912700     EISSN: 15524604     Source Type: Journal    
DOI: 10.1177/0091270009340416     Document Type: Article

References (31)

1. Yusuf S., Zhao F., 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.
2. Chen ZM, Jiang LX, Chen YP Addition of clopidogrel to aspirin in 45,852 patients with acute myocardial infarction: randomised placebo-controlled trial. Lancet. 2005 ; 366: 1607-1621.
3. Sabatine MS, Cannon CP, Gibson CM Addition of clopidogrel to aspirin and fibrinolytic therapy for myocardial infarction with ST-segment elevation. N Engl J Med. 2005 ; 352: 1179-1189.
4. Mehta SR, Yusuf S. Short- and long-term oral antiplatelet therapy in acute coronary syndromes and percutaneous coronary intervention. J Am Coll Cardiol. 2003 ; 41 (suppl S). 79S - 88S.
5. Steinhubl SR, Berger PB, Mann JT III. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002 ; 288: 2411-2420.
6. Buonamici P., Marcucci R., Migliorini A. Impact of platelet reactivity after clopidogrel administration on drug-eluting stent thrombosis. J Am Coll Cardiol. 2007 ; 49: 2312-2317.
7. Gurbel PA, Bliden KP, Samara W. Clopidogrel effect on platelet reactivity in patients with stent thrombosis: results of the CREST Study. J Am Coll Cardiol. 2005 ; 46: 1827-1832.
8. Hochholzer W., Trenk D., Bestehom HP Impact of the degree of peri-interventional platelet inhibition after loading with clopidogrel on early clinical outcome of elective coronary stent placement. J Am Coll Cardiol. 2006 ; 48: 1742-1750.
9. Matetzky S., Shenkman B., Guetta V. Clopidogrel resistance is associated with increased risk of recurrent atherothrombotic events in patients with acute myocardial infarction. Circulation. 2004 ; 109: 3171-3175.
10. 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: 184-194.
11. 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: 357-374.
12. 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.
13. Farid NA, Payne CD, Ernest CS II, et al. Prasugrel, a new thienopyridine antiplatelet drug, weakly inhibits cytochrome P450 2B6 in humans. J Clin Pharmacol. 2008 ; 48: 53-59.
14. Farid NA, McIntosh M., Garofolo F. Determination of the active and inactive metabolites of prasugrel in human plasma by liquid chromatography/ tandem mass spectrometry. Rapid Commun Mass Spectrom. 2007 ; 21: 169-179.
15. Farid NA, Payne CD, Small DS Cytochrome P450 3A inhibition by ketoconazole affects prasugrel and clopidogrel pharmacokinetics and pharmacodynamics differently. Clin Pharmacol Ther. 2007 ; 81: 735-741.
16. Farid NA, Smith RL, Gillespie TA, et al. The disposition of prasugrel, a novel thienopyridine, in humans. Drug Metab Dispos. 2007 ; 35: 1096-1104.
17. Wiviott SD, Antman EM, Winters KJ 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: 3366-3373.
18. Wallentin L., Varenhorst C., James S. 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. 2008 ; 29: 21-30.
19. Wiviott SD, Antman EM, Gibson CM Evaluation of prasugrel compared with clopidogrel in patients with acute coronary syndromes: design and rationale for the TRial to assess Improvement in Therapeutic Outcomes by optimizing platelet InhibitioN with prasugrel Thrombolysis In Myocardial Infarction 38 (TRITON-TIMI 38). Am Heart J. 2006 ; 152: 627-635.
20. Wiviott SD, Braunwald E., McCabe CH Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2007 ; 357: 2001-2015. (Pubitemid 350106708)
21. Small DS, Payne CD, Ferguson-Sells LR Increasing concentrations of prasugrel's active metabolite produce increased inhibition of platelet aggregation. J Am Coll Cardiol. 2006 ; 47 (suppl 1). 379A - 380A.
22. Small DS, Kothare PA, Yuen ES, et al. The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese and Korean subjects compared with healthy Caucasian subjects. Clin Pharmacol Ther. 2008 ; 83 (suppl 1). S56 - S57.
23. Small DS, Wrishko RE, Ernest CS II, et al. Comparison of the pharmacokinetics and pharmacodynamics of prasugrel in subjects with end-stage renal disease and healthy subjects. Presented at: World Conference on Clinical Pharmacology and Therapeutics (CPT); July 27 to August 1, 2008 ; Quebec, Canada.
24. Small DS, Wrishko RE, Ernest CS II, et al. The pharmacokinetics and pharmacodynamics of prasugrel metabolites in elderly healthy subjects. Am J Geriatr Cardiol. 2008 ; 17: 137-143.
25. Ernest CS II, Small DS, Rohatagi S., et al. Population pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel in aspirin-treated patients with stable coronary artery disease. J Pharmacokinet Pharmacodyn. 2008 ; 35: 593-618.
26. 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: 1483-1494.
27. 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: 2553-2560.
28. Mega JL, Close SL, Wiviott SD, et al. Cytochrome P-450 polymorphisms and response to clopidogrel. New Engl J Med. 2009 ; 360: 354-362.
29. Small DS, Payne CD, Kothare PD, et al. Comparison of pharmacokinetics and pharmacodynamics of prasugrel and clopidogrel loading doses in healthy Chinese and Caucasian subjects. Clin Pharmacol Ther. 2008 ; 83 (suppl 1). S56.
30. Small DS, Farid NA, Li YG, et al. Pharmacokinetics and pharmacodynamics of prasugrel in subjects with moderate liver disease. J Clin Pharm Ther. In press.
31. Brandt JT, Payne JT, 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: 66e9-16.