ArticleEuropean journal of clinical pharmacology2012
Vorapaxar, an oral PAR-1 receptor antagonist, does not affect the pharmacokinetics and pharmacodynamics of warfarin.
Article in European journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
3 citing papers in PubMed, 13 citations in OpenAlex.
- Evaluation of pharmacokinetic and pharmacodynamic interactions when lenalidomide is co-administered with warfarin in a randomized clinical trial setting.Clinical drug investigation · 2015Trial
- Vorapaxar: The Current Role and Future Directions of a Novel Protease-Activated Receptor Antagonist for Risk Reduction in Atherosclerotic Disease.Drugs in R&D · 2017Review
- Vorapaxar: first global approval.Drugs · 2014Review
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeVorapaxar 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.
methodsSubjects 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.
resultsThe geometric mean ratio (GMR) as a percentage (warfarin + vorapaxar/warfarin) was calculated. The GMR (90 % CIs) estimates of C(max) were 105 (99, 111) and 105 (99, 112) for R- and S-warfarin, respectively. The GMR (90 % CIs) estimates of AUC(0-∞) were 108 (101, 116) and 105 (96, 115) for R- and S-warfarin, respectively. The GMR (95 % CIs) estimates of AUC(0-120 h) for PT and INR were 97 (95, 98) and 96 (94, 98), respectively.
conclusionResults 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.
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