Pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV inhibitor after oral administration in rats

1. The pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV (DPP IV) inhibitor, was studied in rats after oral administration for developing it as an antidiabetic agent. 2. A liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method was developed to determine lipoyl vildagliptin in rat plasma. After an overnight fasting, rats were orally given lipoyl vildagliptin. Following a single oral dose of 25, 50, and 100 mg.kg(-1), T-max values were from 1.25 to 1.84 h, CL/F values were around 1001 h(-1) kg(-1). In the dose range, C-max values (63.9-296 mu g.l(-1)) and AUC(0-infinity) values (260-1214 mu g.h.l(-1)) were proportional to the,closes. 3. In conclusion, this LC-MS/MS method for the determination of lipoyl vildagliptin in rat plasma was selective and sensitive. In rats, lipoyl vildagliptin displayed linear pharmacokinetics after a single oral dose in the range of 25-100 mg-kg(-1). Lipoyl vildagliptin might have very high CL/F values and V-d/F values, which indicated that the bioavailability of this drug might be low or lipoyl vildagliptin might distribute extensively or accumulate in tissues in view of its high liposolubility.