Pharmacokinetics, pharmacodynamics, and tolerability of single increasing doses of the dipeptidyl peptidase-4 inhibitor alogliptin in healthy male subjects

Clinical Therapeutics
R ChristopherA Karim

Abstract

Alogliptin is a highly selective dipeptidyl peptidase-4 (DPP-4) inhibitor that is under development for the treatment of type 2 diabetes. This study was conducted to characterize the pharmacokinetics, pharmacodynamics, and tolerability of single oral doses of alogliptin in healthy male subjects. This was a randomized, double-blind, placebo-controlled study in which healthy, nonobese male subjects between the ages of 18 and 55 years were assigned to 1 of 6 cohorts: alogliptin 25, 50, 100, 200, 400, or 800 mg. One subject in each cohort received placebo. An ascending-dose strategy was used, in which each cohort received its assigned dose only after review of the safety data from the previous cohort. Blood and urine were collected over 72 hours after dosing for pharmacokinetic analysis and determination of plasma DPP-4 inhibition and active glucagon-like peptide -1(GLP-1) concentrations. Thirty-six subjects (66 per cohort) were enrolled and completed the study (29/36 [81% ] white; mean age, 26.6 years; mean weight, 76.0 kg). Alogliptin was rapidly absorbed (median T(max), 1-2 hours) and eliminated slowly (mean t(1/2), 12.4-21.4 hours), primarily via urinary excretion (mean fraction of drug excreted in urine from 0 to 72 hours afte...Continue Reading

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