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 100?l h^?1 kg^?1. In the dose range, C_max values (63.9–296?μg·l^?1) and AUC_0–∞values (260–1214?μg·h·l^?1) were proportional to the doses.

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.