Concomitant administration of the alpha-glucosidase inhibitor voglibose (AO-128) does not alter the pharmacokinetics of glibenclamide.
OBJECTIVE
Voglibose is a new and potent inhibitor of alpha-glucosidases used for treatment of diabetes mellitus. It increases gastro-intestinal motility and could thus affect absorption of other concurrently administered antidiabetic drugs. The aim of this study was to investigate whether or not voglibose modifies the pharmacokinetics of glibenclamide, a widely used oral antidiabetic, and the glibenclamide-induced decrease in fasting serum glucose.


METHODS
Twelve healthy male subjects were included in this double-blind cross-over study and received a single 1.75-mg dose of glibenclamide on the 8th day of continuous administration of either placebo (reference) or voglibose 5 mg t.i.d. (test). Blood samples were taken to determine the pharmacokinetic characteristics of glibenclamide and the test/reference ratios were evaluated according to bioequivalence criteria. Additional blood samples were taken to measure serum glucose on the same day.


RESULTS
The concentration-time course of glibenclamide under concomitant voglibose administration was similar to that under placebo. The equivalence ratio (test/reference) for the pharmacokinetic characteristics AUCnorm was 1.03 (geometric mean; 0.95-1.11, 90% confidence interval) and Cmax.norm 1.01 (0.94-1.08). The parameters were within the accepted range of 0.8-1.25 (AUC) or 0.7-1.43 (Cmax), thus fulfilling equivalence criteria and indicating no effect of voglibose on glibenclamide kinetics. The glibenclamide-induced decrease in fasting serum glucose concentration was similarly independent of placebo or voglibose co-administration.


CONCLUSIONS
Voglibose did not interact with glibenclamide on a pharmacokinetic level. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.
Kleist
P
P
Takeda Euro R&D Centre GmbH, Hamburger Allee 2-10, Frankfurt/Main, Germany.
Ehrlich
A
A
Suzuki
Y
Y
Timmer
W
W
Wetzelsberger
N
N
Lücker
P W
PW
Fuder
H
H
D000328:Adult; D019540:Area Under Curve; D001786:Blood Glucose / Q000187:drug effects; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005905:Glyburide / Q000097:blood / Q000493:pharmacokinetics*; D065089:Glycoside Hydrolase Inhibitors; D006801:Humans; D007004:Hypoglycemic Agents / Q000097:blood / Q000493:pharmacokinetics*; D007294:Inositol / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male
D001786:Blood Glucose; D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007004:Hypoglycemic Agents; D007294:Inositol; C102817:voglibose; D005905:Glyburide