Clinical Drug Investigation

, Volume 34, Issue 7, pp 449–456 | Cite as

Phase 1 Study of the Effect of Icosapent Ethyl on Warfarin Pharmacokinetic and Anticoagulation Parameters

  • Rene A. Braeckman
  • William G. Stirtan
  • Paresh N. Soni
Original Research Article

Abstract

Background and Objective

Icosapent ethyl (IPE) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved to reduce triglyceride levels in patients with severe (≥5.65 mmol/L) hypertriglyceridemia. EPA, the active metabolite of IPE, is mainly metabolized via β-oxidation, and studies suggest that omega-3 fatty acids such as EPA may have antithrombotic effects. The objective of this study was to evaluate the effect of IPE on the pharmacokinetic and anticoagulation pharmacodynamics of warfarin, a substrate of cytochrome P450 2C9-mediated metabolism.

Methods

Healthy adults received oral warfarin (25 mg) on day 1, oral IPE (4 g/day) on days 8–35, and co-administration on Day 29. Primary pharmacokinetic end points were area under the concentration-versus-time curve from zero to infinity (AUC0–∞) and maximum plasma concentration (Cmax) for R- and S-warfarin; pharmacodynamic end points were area under the international normalized ratio (INR) effect-time curve after the warfarin dose (AUCINR) and maximum INR (INRmax).

Results

Twenty-five subjects completed the study. AUC0–∞ and Cmax ratios of geometric means for both R- and S-warfarin following co-administration of warfarin with versus without IPE were within the 90 % confidence intervals of 0.80–1.25. AUCINR, INRmax, and ratios were also similar.

Conclusions

IPE 4 g/day did not significantly change the single-dose AUC0–∞ or Cmax of R- and S-warfarin or the anticoagulation pharmacodynamics of warfarin when co-administered as racemic warfarin at 25 mg. Co-administration of these drugs was safe and well tolerated in this study of healthy adult subjects.

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Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • Rene A. Braeckman
    • 1
  • William G. Stirtan
    • 1
  • Paresh N. Soni
    • 1
  1. 1.Amarin Pharma Inc.BedminsterUSA

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