Dose Proportionality and the Effect of Food on Vildagliptin, a Novel Dipeptidyl Peptidase IV Inhibitor, in Healthy Volunteers.

Vildagliptin is a potent and selective dipeptidyl peptidase IV inhibitor in development for the treatment of type 2 diabetes that improves glycemic control by enhancing α- and β-cell responsiveness to glucose. Two open-label, single-dose, randomized, crossover studies in healthy subjects (ages 18-45 years) investigated the dose proportionality of vildagliptin pharmacokinetics (n = 20) and the effect of food (n = 24) on vildagliptin pharmacokinetics. There was a linear relationship (r² = 0.999) between vildagliptin doses of 25, 50, 100, and 200 mg and area under the plasma concentration-time curve from time zero to infinity (AUC_0-∞) and maximum plasma concentration (C_max). Dose proportionality was assessed using a statistical power model [X = α·(dose)^β]. The 90% confidence intervals of the proportionality coefficient, β, for A UC_0-∞, (1.15-1.19) and C_max (1.04-1.1 4) indicated that deviations from dose proportionality were small (<7.7%). Doubling of dose led to 2.1- to 2.3-fold increases in AUC_0-∞ and C_max but no dose-dependent changes in time to reach C_max or terminal elimination half-life. Administration of vildagliptin 100 mg following a high-fat meal decreased C_max by 19% and AUC_0-∞ by 10%. Vildagliptin displays approximately dose-proportional pharmacokinetics over the 25- to 200-mg dose range, and administration with food has no clinically relevant effect on vildagliptin pharmacokinetics. [ABSTRACT FROM AUTHOR]