PIII‐61

BACKGROUND/AIMS Exenatide, a new therapy for the treatment of type 2 diabetes, slows gastric emptying as one of its actions and therefore may alter the absorption of concomitant oral drugs. This study evaluated the influence of exenatide co‐administration on the PK and PD of warfarin. METHODS 15 healthy male subjects (22–50 yr, BMI 19.0–27.5 kg/m 2 ) participated in this open‐label, two‐period, fixed‐sequence study. Each subject received a single, 25‐mg, oral dose of warfarin in Period 1 and concomitantly with 10 μg exenatide SC BID in Period 2. Serial sampling for plasma warfarin concentrations and coagulation index (INR) were conducted up to 144 hr post dose. RESULTS Exenatide did not produce statistically significant changes in R‐ or S‐warfarin AUC 0‐∞ or C max . For R‐warfarin, the ratios (exenatide/no exenatide) of AUC 0‐∞ and C max geometric means (90% CI) were 1.11 (1.06–1.17) and 1.05 (1.00–1.09) respectively and for S‐warfarin, 1.06 (1.01–1.11) and 0.97 (0.93–1.01). Exenatide also produced no significant changes in INR AUC or INR max ; the ratios of geometric means were 0.94 (0.93–0.96) and 0.88 (0.84–0.92) respectively. The most frequent adverse events were mild to moderate nausea, somnolence, and headache; no hypoglycemic events occurred. CONCLUSIONS Co‐administration of warfarin with exenatide was generally well tolerated and resulted in no significant changes in warfarin PK or in INR. These results indicate that no adjustment in INR monitoring or warfarin dosage is required with exenatide. Clinical Pharmacology & Therapeutics (2005) 79 , P75–P75; doi: 10.1016/j.clpt.2005.12.269