PII-12Absolute bioavailability of vildagliptin in healthy subjects

OBJECTIVES Vildagliptin (V) is a potent and specific DPP-4 inhibitor, which is developed for treatment of type 2 diabetes (T2D). The objective of this study was to investigate the absolute bioavailability (F) of V after oral and intravenous (iv) administration of V. METHODS This was an open label, single-dose, randomized, cross-over study in healthy volunteers. Thirteen subjects were enrolled and 12 completed the study. Each subject was randomly assigned to receive one of the two treatments in a sequential manner with 72-hr interval between treatment periods: 50 mg po or 25 mg iv infusion over 30 minutes. Blood samples were collected after oral and iv administrations and the concentrations were measured by LC-MS/MS. RESULTS The absolute oral F of V was estimated to be 85% with a 90% confidence interval over the range between 79 and 91%. After iv infusion, the total body clearance (CLtot) and the renal clearance (CLR) were 40.6±8.97 L/hr and 13.0±2.35 L/hr, respectively, demonstrating that CLRaccounted for 33% of the CLtot. The volume of distribution at steady-state was 70.5±16.1 L, suggesting that V distributes into tissues and organs. CONCLUSIONS The oral absolute F of V was 85%. The total recovery of radioactivity in urine when[14C]-V was given orally in a previous study was also ∼85%, suggesting that hepatic excretion has little contribution to the elimination of V. Single oral and iv administrations of V were well tolerated in this small number of healthy subjects. Clinical Pharmacology & Therapeutics (2005) 79, P38–P38; doi: 10.1016/j.clpt.2005.12.137