OBJECTIVE: Voglibose is a new and potent inhibitor of alpha-glucosidases 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 not voglibose modifies the pharmacodynamics and pharmacokinetics of warfarin, an oral anticoagulant frequently used in cardiovascular disorders likely to arise in diabetic patients. METHODS: Twelve healthy male subjects were given individually adjusted doses of warfarin to reduce prothrombin time (Quick's method) to a value of about 30-40% of the normal range within the first 8 days. Then, the individuals maintenance dose, given in the morning, was maintained until day 15. On study days 11-15, voglibose was co-administered per os in a dose of 5 mg t.i.d. The prothrombin time was determined on days 10 and 11 (reference) and on days 15 and 16 (test), and the steady-state pharmacokinetic characteristics of the warfarin enantiomers were determined on days 10 (reference) and 15 (test). The ratios test/reference were evaluated according to bioequivalence criteria. RESULTS: The equivalence ratio (test reference) for the pharmacodynamic parameter prothrombin time was 0.97 and for the pharmacokinetic characteristics AUC0-24 h.t.ss: S-(-)-warfarin, 1.05; R-(+)-warfarin, 1.01; and Cmax.ss: S-(-)-warfarin, 1.08; R-(+)-warfarin, 1.04. All parameters were within the predetermined accepted range of 0.7-1.43 (pharmacodynamics) or 0.8-1.25 (pharmacokinetics), thus fulfilling equivalence criteria. CONCLUSIONS: Voglibose modified neither the pharmacodynamics nor the pharmacokinetics of warfarin under steady-state conditions. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.
OBJECTIVE:Voglibose is a new and potent inhibitor of alpha-glucosidases and is used for the treatment of diabetes mellitus. Since vogliboseincreases gastrointestinal motility and could thus affect absorption of concomitantly administered drugs, it was investigated whether or not voglibose modifies the pharmacodynamics and pharmacokinetics of warfarin, an oral anticoagulant frequently used in cardiovascular disorders likely to arise in diabeticpatients. METHODS: Twelve healthy male subjects were given individually adjusted doses of warfarin to reduce prothrombin time (Quick's method) to a value of about 30-40% of the normal range within the first 8 days. Then, the individuals maintenance dose, given in the morning, was maintained until day 15. On study days 11-15, voglibose was co-administered per os in a dose of 5 mg t.i.d. The prothrombin time was determined on days 10 and 11 (reference) and on days 15 and 16 (test), and the steady-state pharmacokinetic characteristics of the warfarin enantiomers were determined on days 10 (reference) and 15 (test). The ratios test/reference were evaluated according to bioequivalence criteria. RESULTS: The equivalence ratio (test reference) for the pharmacodynamic parameter prothrombin time was 0.97 and for the pharmacokinetic characteristics AUC0-24 h.t.ss: S-(-)-warfarin, 1.05; R-(+)-warfarin, 1.01; and Cmax.ss: S-(-)-warfarin, 1.08; R-(+)-warfarin, 1.04. All parameters were within the predetermined accepted range of 0.7-1.43 (pharmacodynamics) or 0.8-1.25 (pharmacokinetics), thus fulfilling equivalence criteria. CONCLUSIONS:Voglibose modified neither the pharmacodynamics nor the pharmacokinetics of warfarin under steady-state conditions. Concomitant treatment was well tolerated and has been proven to be safe for further clinical use.