Pharmacokinetics of lipoyl vildagliptin, a novel dipeptidyl peptidase IV inhibitor after oral administration in rats.
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. 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 x 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 x l(-1)) and AUC(0-∞)values (260-1214 μg x h x l(-1)) were proportional to the doses. 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 x 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.
Wang
X
X
College of Pharmacy, Shandong University, Jinan, P.R. China.
Zhang
D
D
Xu
W
W
Liu
H
H
Wang
W
W
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000284:Administration, Oral; D000818:Animals; D002853:Chromatography, Liquid; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D009570:Nitriles / Q000008:administration & dosage / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D008063:Thioctic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D009570:Nitriles; D011759:Pyrrolidines; C554665:lipoyl vildagliptin; D008063:Thioctic Acid; D000077597:Vildagliptin; D000218:Adamantane