Retrospective and Prospective Human Intravenous and Oral Pharmacokinetic Projection of Dipeptidyl peptidase-IV Inhibitors Using Simple Allometric Principles - Case Studies of ABT-279, ABT-341, Alogliptin, Carmegliptin, Sitagliptin and Vildagliptin.

摘要: Purpose: The purpose of this exercise was to explore the utility allometric scaling approach for prediction intravenous and oral pharmacokinetics six dipeptidy peptidase-IV (DPP-IV) inhibitors viz. ABT-279, ABT-341, alogliptin, carmegliptin, sitagliptin vildagliptin. Methods: availability pharmacokinetic data in animals enabled allometry 6 DPP-IV inhibitors.  relationship between main parameters [viz. volume distribution (V d ) clearance (CL)] body weight studied across three or four mammalian species, using double logarithmic plots predict human CL V simple allometry.  Results: A simply relationship: Y = aW b found be adequate clearance/volume inhibitors. equations sitagliptin, vildagliptin, ABT-279 ABT-341 were 1.867W 0.780 , 1.170W 0.756 2.020W 0.529 1.959 W 0.847 0.672 1.016 1.077W 0.649 respectively, (CL) corresponding were: 3.313W 0.987 6.096W 0.992 7.140W 0.805 2.742W 0.941 1.299W 0.695 5.370W 0.803 .  With exception a few discordant values exponent rule appeared hold (0.75) (1.0) predictions various Regardless routes, predicted within 2-3 fold observed better than Conclusion: Simple retrospectively with reasonable accuracy reported gliptins could used as prospective tool class drugs. This article is open POST-PUBLICATION REVIEW . Registered readers (see “For Readers”) may comment by clicking on ABSTRACT issue’s contents page.