Dose-proportionality of a final market image sitagliptin formulation, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers.

Abstract

Sitagliptin is a highly selective orally active dipeptidyl peptidase-4 inhibitor recently approved in the United States for the treatment of type 2 diabetes. Ten healthy subjects received single oral doses of 25, 50, 100, 200 and 400 mg final market image tablets in five separate treatment periods in randomized fashion to assess dose proportionality. Blood (up to 72 h post-dose) and urine (up to 24 h post-dose) samples for sitagliptin pharmacokinetic analysis were collected at pre-specified times following administration of sitagliptin. Dose-proportionality of AUC(0-infinity), C(max) and C(24 h) was assessed using a power-law model. The results of this study indicate that plasma AUC(0-infinity) increased in a dose-proportional manner over the 25-400 mg dose range. Over the same dose range, plasma C(max) increased in a greater than dose-proportional manner and C(24 h) increased in a modestly less than dose proportional manner. No clinically meaningful differences in T(max) or apparent t(1/2) were noted across the dose range. Differences in the percentage of the sitagliptin dose excreted unchanged in urine (72.5% pooled across doses) and renal clearance (344 ml/min pooled across doses) were not statistically significant. Sitagliptin was generally well tolerated at all the doses evaluated.

Cite this paper

@article{Bergman2007DoseproportionalityOA, title={Dose-proportionality of a final market image sitagliptin formulation, an oral dipeptidyl peptidase-4 inhibitor, in healthy volunteers.}, author={Arthur J. Bergman and Goutam C Mistry and Wen-lin Luo and Qingliang Liu and Julie Stone and Amy Wang and Wei Zeng and Li Chen and Stacy C. Dilzer and Kenneth C . Lasseter and Gary A. Herman and John A. Wagner and Rajesh Krishna}, journal={Biopharmaceutics & drug disposition}, year={2007}, volume={28 6}, pages={307-13} }