THE ALPHA-GLUCOSIDASE INHIBITOR VOGLIBOSE (AO-128) DOES NOT CHANGE PHARMACODYNAMICS OR PHARMACOKINETICS OF WARFARIN

Objective: Voglibose is a new and potent inhibitor of alpha-glucosidas es and is used for the treatment of diabetes mellitus. Since voglibose increases gastrointestinal motility and could thus affect absorption of concomitantly administered drugs, it was investigated whether or no t voglibose modifies the pharmacodynamics and pharmacokinetics of warf arin, an oral anticoagulant frequently used in cardiovascular disorder s likely to arise in diabetic patients. Methods: Twelve healthy male s ubjects were given individually adjusted doses of warfarin to reduce p rothrombin time (Quick's method) to a value of about 30-40% of the nor mal range within the first 8 days. Then, the individual maintenance do se, given in the morning, was maintained until day 15. On study days 1 1-15, voglibose was co-administered per os in a dose of 5 mg t.i.d. Th e prothrombin time was determined on days 10 and 11 (reference) and on days 15 and 16 (test), and the steady-state pharmacokinetic character istics of the warfarin enantiomers were determined on days 10 (referen ce) and 15 (test). The ratios test/reference were evaluated according to bioequivalence criteria. Results: The equivalence ratio (test/refer ence) for the pharmacodynamic parameter prothrombin time was 0.97 and for the pharmacokinetic characteristics AUC(0-24) h, tau, ss: S-(-)-wa rfarin, 1.05; R-(+)-warfarin, 1.01; and C-max,C-ss: S-(-)-warfarin, 1. 08; R-(+)-warfarin,l.04. All parameters were within the predetermined accepted range of 0.7-1.43 (pharmacodynamics) or 0.8-1.25 (pharmacokin etics), thus fulfilling equivalence criteria. Conclusions: Voglibose m odified neither the pharmacodynamics nor the pharmacokinetics of warfa rin under steady-state conditions. Concomitant treatment was well tole rated and has been proven to be safe for further clinical use.