Pharmacokinetics and pharmacodynamics of vildagliptin in Japanese patients with Type 2 diabetes

OBJECTIVE: To assess the pharmacokinetics, pharmacodynamics and safety of vildagliptin, a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-4), in Japanese patients with Type 2 diabetes. METHODS: In this randomized, double-blind, placebo-controlled, parallel-group study, 62 Japanese patients with Type 2 diabetes received vildagliptin 10 mg, 25 mg or 50 mg twice daily for 7 days. Blood samples were collected for the determination of plasma concentrations of vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1), glucose, insulin and glucagon. RESULTS: Exposure to vildagliptin (area under the plasma concentration-time curve from 0 to 12 h (AUC0-12h) and the maximum plasma concentration (Cmax)) increased in an approximately dose-proportional manner, and no accumulation was observed following multiple doses of vildagliptin (accumulation factor 1.00 - 1.02). DPP-4 activity was completely inhibited for varying durations by all doses of vildagliptin; the duration of complete DPP-4 inhibition was dose-dependent. DPP-4 inhibition after vildagliptin 50 mg twice daily remained > 80% throughout the 24-h period. Vildagliptin treatment led to a dose-dependent increase in plasma active GLP-1 levels; the overall increases (area under the effect-time course from 0 to 8 h, AUE0-8h) after 7 days' treatment were 1.5-, 1.7-, and 1.8-fold with vildagliptin 10 mg, 25 mg and 50 mg twice daily, respectively (all p < 0.0001 vs. placebo). Postprandial plasma glucose during the 4-h period after breakfast was significantly reduced with the 10, 25 and 50 mg vildagliptin doses by 50.3, 92.2 and 69.5 mg·h/dl, respectively. Insulin levels remained unchanged in the context of reduced glucose levels at all doses studied. CONCLUSIONS: Vildagliptin demonstrated similar pharmacokinetic and pharmacodynamic effects in Japanese patients to those observed previously in non-Japanese patients with Type 2 diabetes.