Effect of food on the pharmacokinetics of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet in healthy volunteers.
OBJECTIVE
Vildagliptin is an orally active, potent and selective DPP-4 inhibitor that improves glycemic control in patients with type 2 diabetes by increasing alpha- and beta-cell responsiveness to glucose.


METHODS
This open-label, single-center, randomized, two-period crossover study in healthy subjects (n=23) ages 18-45 years investigated the effect of food on the pharmacokinetics of vildagliptin and metformin following administration of a vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet.


RESULTS
Administration of the fixed-dose combination tablet following a high-fat meal had no effect on vildagliptin AUC(0-infinity) (ratio of geometric mean for fed:fasted state, 1.10 [90% CI 1.03, 1.18]), C(max) (ratio of means 0.98 [90% CI 0.85, 1.13]) or median t(max) (2.5 h in fed and fasted states). The rate of absorption of metformin was decreased when given with food, as reflected by the prolonged t(max) (2-4 h) and reduction in C(max) (by 26%), but the extent of absorption was not changed. The food effect on the metformin component of the fixed-dose combination tablets was consistent with, but of a lesser magnitude compared with data stated.


CONCLUSIONS
The vildagliptin/metformin (50/1000 mg) fixed-dose combination tablet can be administered in the same manner as metformin, and can be recommended to be taken with meals to reduce the gastrointestinal symptoms associated with metformin.
He
Yan-Ling
YL
Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
Flannery
Brian
B
Campestrini
Joelle
J
Leon
Selene
S
Zinny
Miguel A
MA
Ligueros-Saylan
Monica
M
Jarugula
Venkateswar
V
D000218:Adamantane / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000293:Adolescent; D000328:Adult; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology* / Q000627:therapeutic use; D004338:Drug Combinations; D005260:Female; D018565:Food-Drug Interactions; D006801:Humans; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D008875:Middle Aged; D009570:Nitriles / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011759:Pyrrolidines / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D000077597:Vildagliptin
D054873:Dipeptidyl-Peptidase IV Inhibitors; D004338:Drug Combinations; D009570:Nitriles; D011759:Pyrrolidines; D008687:Metformin; D000077597:Vildagliptin; D000218:Adamantane