Equipotent inhibition of gastric acid secretion by equal doses of oral or intravenous pantoprazole.

BACKGROUND: Pantoprazole is a proton pump inhibitor characterized by a low potential to interact with the cytochrome P450 system, and linear pharmacokinetics. The recommended oral dose for treatment of acid-related diseases is 40 mg. METHODS: Using a randomized, crossover study design we compared the ability of 40 mg oral and intravenous pantoprazole to elevate the intragastric pH in healthy volunteers (n = 20, 'per protocol'), during two treatment phases. The duration of each phase was 5 days. Pantoprazole 40 mg was administered once daily either as a tablet or as an intravenous injection. A 24 h pHmetry was used to record the intragastric pH on day 5 of each regimen; this was compared to the baseline curve obtained before each study period. The calculated 90% confidence intervals (90% CI) represent the mean difference in the intragastric pH, attained after intravenous or oral administration. The predefined equivalence range for the 90% CI was +/- 20% for the percentage time at which the gastric pH was at least pH 3 or 4 and +/- 1 unit for the median pH. RESULTS: Pantoprazole was well tolerated during both treatment phases. The mean of the 24 h median pH was 3.3 and 3.1 for the intravenous and oral treatments, respectively; the corresponding differences were 0.2 (90% CI: - 0.03 to 0.44). For the mean percentage time at which the pH was 3 or above, the respective calculated values were 57% and 51%, with a difference between the two administration routes of only 5.7% (90% CI: 1.8 to 9.6). At an intragastric pH of 4 or above, the mean percentage time was 420% and 38% following intravenous and oral treatment, respectively, with a difference between the treatment routes of only 4.4% (90% CI: 0.6 to 8.3). CONCLUSIONS: These results imply that the two formulations of pantoprazole can be assumed to be equipotent. Hence, the intravenous formulation of pantoprazole could be considered as an alternative route of administration.

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-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.