Bioequivalence study of a novel Solutab tablet formulation of amoxicillin/clavulanic acid versus the originator film-coated tablet.
With amoxicillin/clavulanic acid Solutab tablet, a new tablet formulation of amoxicillin/clavulanic acid (500/125), was developed. The aim of the present study was to demonstrate bioequivalence between the new tablet formulation, taken as an intact tablet and after prior dispersal, versus the originator product viz. Augmentan film-coated tablet. The study was performed in 48 healthy volunteers, according to an open, single-dose three-period, crossover design. Blood samples were taken prior to each administration and at 10 time points after dosing. Plasma concentrations of amoxicillin and clavulanic acid were determined by validated high performance liquid chromatography with UV detection. With regard to amoxicillin, the results were within the preset bioequivalence range of 0.8 to 1.25 for the ratios of the primary parameters AUC(0-t) and Cmax. In terms of clavulanic acid the 90% confidence intervals of the ratios for AUC(0-t) and Cmax versus the reference lay outside the predefined bioequivalence range of 0.75 to 1.33. This result, however, was mainly due to the large variability of the reference formulation compared to the amoxicillin/clavulanic acid Solutab tablet. Based on statistical indications that 3/48 subjects with extremely low levels on the reference formulation could be regarded as "outliers" and after excluding these subjects' data from the statistical analysis, results for clavulanic acid were within the predefined bioequivalence range of 0.75 to 1.33. Overall, the amoxicillin/clavulanic acid Solutab tablet provided, in comparison to the reference tablet, less variable levels of clavulanic acid, thus giving more appropriate protection to the available amoxicillin. Thirteen adverse events were reported post dosing by 7 subjects. There were no differences in incidence of adverse events between amoxicillin/clavulanic acid Solutab tablet taken intact or dispersed and Augmentan.
University of Münster, Germany.
H
H
Sourgens
H
H
Steinbrede
J S
JS
Verschoor
M A
MA
Bertola
B
B
Rayer
D000293:Adolescent; D000328:Adult; D000658:Amoxicillin / Q000097:blood / Q000493:pharmacokinetics*; D000900:Anti-Bacterial Agents / Q000097:blood / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002851:Chromatography, High Pressure Liquid; D019818:Clavulanic Acid / Q000097:blood / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D004338:Drug Combinations; D004339:Drug Compounding; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D013607:Tablets / Q000493:pharmacokinetics; D013608:Tablets, Enteric-Coated / Q000493:pharmacokinetics; D013810:Therapeutic Equivalency
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D013607:Tablets; D013608:Tablets, Enteric-Coated; D019818:Clavulanic Acid; D000658:Amoxicillin