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.
He
Y-L
YL
Novartis Institutes for Biomedical Research Inc., Cambridge, MA, USA. yanling.he@novartis.com
Yamaguchi
M
M
Ito
H
H
Terao
S
S
Sekiguchi
K
K
D000218:Adamantane / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D000328:Adult; D000368:Aged; D019540:Area Under Curve; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000493:pharmacokinetics*; D004311:Double-Blind Method; D005260:Female; D005934:Glucagon / Q000097:blood; D052216:Glucagon-Like Peptide 1 / Q000097:blood; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009570:Nitriles / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011759:Pyrrolidines / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D007328:Insulin; D009570:Nitriles; D011759:Pyrrolidines; D052216:Glucagon-Like Peptide 1; D005934:Glucagon; D000077597:Vildagliptin; D000218:Adamantane