Influence of acarbose on blood glucose and breath hydrogen after carbohydrate load with sucrose or starch.

A monocentric, open, randomised, single-dose, six-period crossover trial was carried out in healthy volunteers under fasting conditions to establish the most appropriate study design for a pivotal bioequivalence trial with acarbose (CAS 56180-94-0) regarding a) dosage of the drug, b) type of carbohydrate load, c) type of primary endpoint, and d) sample size. 50 g sucrose or 50 g starch were used as carbohydrate load. Acarbose was administered in doses of 50 and 200 mg. Blood glucose and breath hydrogen were evaluated as endpoints. Both acarbose doses reduced the effect of carbohydrate load. Blood glucose: no statistically significant difference could be noted between the overall effect of 50 mg and that of 200 mg acarbose irrespective of the type of carbohydrate load. Breath hydrogen: an influence could be shown only for sucrose as carbohydrate load. Practically no effect was observed with starch. The overall increase of effect is by more than 200% with sucrose when the dose of acarbose increases from 50 to 200 mg. This difference between the effects of both doses of acarbose on breath hydrogen is statistically significant. For a pivotal trial, sucrose is the most appropriate type of carbohydrate load, baseline adjusted area under the breath hydrogen response is the most appropriate primary endpoint, and a dose of 100 mg acarbose is the most appropriate dosage. A total number of 100 subjects will be needed for proving pharmacodynamic equivalence between two acarbose products in a pivotal trial.

Effect of the formulation on the bioequivalence of sultamicillin: tablets and suspension.

Sultamicillin (CAS 76497-13-7) is a pro-drug of a combination of ampicillin and sulbactam linked as a double ester. The aim of the present studies, performed in two different groups of volunteers, was to compare the bioavailability of 750 mg sultamicillin tablets (Duobaktam 750 mg tablets, study 1) and sultamicillin 250 mg/5mL suspensions (Duobaktam 250 mg/5mL, study 2). Each study was conducted according to an open, randomized, single-dose, two-period cross-over design in 24 healthy volunteers with a wash-out period from 7 to 14 days. Blood samples were taken up to 12 h post dosing, and concentrations of ampicillin and sulbactam were determined by a HPLC-UV method. In the first study, the 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of ampicillin and sulbactam were between 1.01-1.18 and 0.95-1.09 (AUC0-t) as well as between 0.87-1.04 and 0.80-0.96 (Cmax), respectively, and thus within the acceptance ranges. The 90% confidence interval for intra-individual ratios of AUC0-t and Cmax of sultamicillin suspensions (2nd study) were between 0.94-1.16 (ampicillin) and 0.92-1.14 (sulbactam) for AUC0-t and between 0.96-1.23 (ampicillin) and 0.97-1.24 (sulbactam) for Cmax. These values were also within the acceptance range for bioequivalence studies. Concerning the secondary parameter tmax the 90%-confidence interval for the intra-individual differences for both ampicillin and sulbactam were between 0.00-0.50 in the first and between -0.17-0.00 in the second study, respectively. In the light of the present studies it can be concluded that the sultamicillin test formulations, i.e. tablet and suspension are bioequivalent to the respective reference formulations.