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- Title
Vorapaxar, an oral PAR-1 receptor antagonist, does not affect the pharmacokinetics and pharmacodynamics of warfarin.
- Authors
Kosoglou, Teddy; Zhu, Yali; Xuan, Fengjuan; Black, Laura; Johnson-Levonas, Amy; Martinho, Monika; Statkevich, Paul; Cutler, David
- Abstract
Purpose: Vorapaxar is an orally active protease-activated receptor 1 (PAR-1) antagonist that inhibits thrombin-induced platelet aggregation. This open-label study assessed the pharmacokinetics and pharmacodynamics of single-dose warfarin in the presence/absence of multiple-dose vorapaxar in 12 healthy men. Methods: Subjects received two treatments separated by ≥7-day washout: Treatment A warfarin 25 mg (Day 1); Treatment B vorapaxar 2.5 mg/day on Days 1-6 and vorapaxar 40 mg coadministered with warfarin 25 mg (Day 7). R-warfarin, S-warfarin, and prothrombin time (PT) were assayed predose and up to 120 h postdose. Results: The geometric mean ratio (GMR) as a percentage (warfarin + vorapaxar/warfarin) was calculated. The GMR (90 % CIs) estimates of C were 105 (99, 111) and 105 (99, 112) for R- and S-warfarin, respectively. The GMR (90 % CIs) estimates of AUC were 108 (101, 116) and 105 (96, 115) for R- and S-warfarin, respectively. The GMR (95 % CIs) estimates of AUC for PT and INR were 97 (95, 98) and 96 (94, 98), respectively. Conclusion: Results of this study indicate that vorapaxar has no meaningful effect on the pharmacokinetics or pharmacodynamics of warfarin, suggesting that the coadministration of these two drugs or vorapaxar coadministered with other CYP2C9/CYP2C19 substrates is unlikely to cause a clinically significant pharmacokinetic drug interaction.
- Subjects
KANSAS; PLATELET aggregation inhibitors; ANALYSIS of variance; CONFIDENCE intervals; DRUG interactions; REGRESSION analysis; RESEARCH funding; WARFARIN; DATA analysis software; DESCRIPTIVE statistics; PHARMACODYNAMICS; THERAPEUTICS
- Publication
European Journal of Clinical Pharmacology, 2012, Vol 68, Issue 11, p1509
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-012-1271-0