Abstract
Background
Vorapaxar, a novel antiplatelet agent in advanced clinical development for the prevention and treatment of atherothrombotic disease, is a potent, orally bioavailable thrombin receptor antagonist selective for the protease-activated receptor 1 (PAR-1).
Methods
Since race/ethnicity may affect the safety, efficacy and dosage of drugs, this study was conducted to evaluate potential differences in the pharmacodynamics, pharmacokinetics and safety of vorapaxar after single (5, 10, 20, or 40 mg) or multiple (0.5, 1, or 2.5 mg once daily) doses in healthy Japanese and matched (gender, age, height, and weight) Caucasian volunteers.
Results
Vorapaxar was well tolerated in both Japanese and Caucasian subjects. Pharmacodynamic and pharmacokinetic profiles of vorapaxar in the two racial/ethnic groups were similar. In both racial groups, complete inhibition of platelet aggregation was achieved most rapidly with vorapaxar 40 mg and was consistently achieved and maintained with a 2.5 mg daily maintenance dose.
Conclusion
There were no substantial differences in the safety, pharmacokinetics or pharmacodynamics of vorapaxar between Japanese and Caucasian subjects.
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Acknowledgments
The authors thank Joshua Barbach and Sean Gregory for editorial support of the manuscript. This assistance was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA. The authors also wish to thank Sharon Byrnes (Merck Sharp & Dohme Corp.) for editorial support and assisting with the preparation of this manuscript for submission and publication.
Funding
This study was supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA.
Conflict of interest statement
T. Kosoglou, L. Reyderman, C. Kasserra, S. Young, J. Pei, S.E. Maxwell, J. Schiller, A.G. Meehan, and D.L. Cutler all declare that they are/were employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA, at the time of the study. The current affiliation for L. Reyderman is Eisai Inc., Ridgefield Park, NJ, USA. The current affiliation for C. Kasserra and S.E. Maxwell is Celgene Corp., Summit, NJ, USA. L.K. Jennings received research grant support from Schering-Plough Corporation (now Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA).
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Kosoglou, T., Reyderman, L., Kasserra, C. et al. No differences in the pharmacodynamics and pharmacokinetics of the thrombin receptor antagonist vorapaxar between healthy Japanese and Caucasian subjects. Eur J Clin Pharmacol 68, 291–300 (2012). https://doi.org/10.1007/s00228-011-1127-z
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DOI: https://doi.org/10.1007/s00228-011-1127-z