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-glucosidas es used for treatment of diabetes mellitus. It increases gastro-intest inal motility and could thus affect absorption of other concurrently a dministered antidiabetic drugs. The aim of this study was to investiga te whether or not voglibose modifies the pharmacokinetics of glibencla mide, a widely used oral antidiabetic, and the glibenclamide-induced d ecrease in fasting serum glucose. Methods: Twelve healthy male subject s were included in this double-blind cross-over study and received a s ingle 1.75-mg dose of glibenclamide on the 8th day of continuous admin istration of either placebo (reference) or voglibose 5 mg t.i.d. (test ). Blood samples were taken to determine the pharmacokinetic character istics of glibenclamide and the test/reference ratios were evaluated a ccording to bioequivalence criteria. Additional blood samples were tak en to measure serum glucose on the same day. Results: The concentratio n-time course of glibenclamide under concomitant voglibose administrat ion was similar to that under placebo. The equivalence ratio (test/ref erence) for the pharmacokinetic characteristics AUC(norm) was 1.03 (ge ometric mean; 0.95-1.11, 90% confidence interval) and C-max,C-norm 1.0 1 (0.94-1.08). The parameters were within the accepted range of 0.8-1. 25 (AUC) or 0.7-1.43 (C-max), thus fulfilling equivalence criteria and indicating no effect of voglibose on glibenclamide kinetics. The glib enclamide-induced decrease in fasting serum glucose concentration was similarly independent of placebo or voglibose co-administration. Concl usions: Voglibose did not interact with glibenclamide on a pharmacokin etic level. Concomitant treatment was well tolerated and has been prov en to be safe for further clinical use.