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Effect of Exenatide on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Asian Men

From Lilly-NUS Centre for Clinical Pharmacology, Singapore (Dr Soon, Ms Yuen, Dr Wise); Eli Lilly and Company, Indianapolis, Indiana (Dr Kothare, Dr Park, Dr Mace); and Eli Lilly and Company, Windlesham, United Kingdom (Dr Linnebjerg).

Exenatide, a treatment for type 2 diabetes, slows gastric emptying as part of its pharmacologic action and may alter the absorption of concomitant oral drugs. This open-label, 2-period, fixed-sequence study evaluated the influence of exenatide coadministration on the pharmacokinetics and pharmacodynamics of warfarin, a narrow therapeutic index drug, in healthy men (N = 16). A single, 25-mg oral dose of warfarin, with a standardized breakfast, was administered alone in period 1 and concomitantly with 10 µg exenatide subcutaneous twice daily in period 2. Exenatide did not produce significant changes in R- or S-warfarin pharmacokinetics. Although there were minor reductions in warfarin anticoagulant effect, the ratios of geometric means for the area under the international normalized ratio (INR)–time curve from dosing until the time of the last measurable INR value or maximum-observed INR response being 0.94 (0.93-0.96) and 0.88 (0.84-0.92), respectively, the magnitude and direction of these changes do not suggest a safety concern from this interaction.

Key Words: Exenatide • warfarin • drug interaction • international normalized ratio

Address for reprints: Danny Soon, MBBS, Lilly-NUS Centre for Clinical Pharmacology, Level 6, Clinical Research Centre, MD 11, National University of Singapore, 10 Medical Drive, Singapore 117597, Singapore; e-mail: soon_danny{at}lilly.com.