Pharmacokinetics and bioequivalence study of 500 milligram dicloxacillin capsules in healthy Thai volunteers

Abstract

Three brands of 500 mg dicloxacillin capsules were evaluated. In vitro studies indicated that all brands met the general requirements of the United States Pharmacopoeia 24 for content of active ingredient and uniformity of dosage units. Dissolution profile studies revealed that each curve of local brand (B and C) was similar to that of innovatorʼs product (A). Comparative bioavailability of 500 mg dicloxacillin capsule of brands B and C relative to brand A was conducted in 15 healthy Thai male volunteers using a single dose of 2x500 mg capsules in a three way crossover design. Blood samples were collected at appropriate time interval. Serum dicloxacillin concentrations were determined via high performance liquid chromatography. Individual serum dicloxacillin concentration-time profile was analyzed for relevant pharmacokinetic parameters. Data analysis revealed that there were no statistically significant differences (p>0.05) among the corresponding logarithmically transformed pharmacokinetic parameters; AUC and C[subscript max] values of all three brands. Also, the ratios of individual parameter based on log-transformed data of brands B and C to that of brand A were within 80-125 % of 90% confidence interval. These implied that brands B and C were bioequivalent with brand A in terms of both the rate and amount (extent) of drug absorption. The pharmacokinetics of 500 mg dicloxacillin capsule was described by one compartment open model with first order absorption and first order elimination. Time to peak serum concentrations was between 1.35 to 1.60 hr, the absorption rate constants were between 1.44 to 1.62 hr-1, the eliminate rate constants were within 0.53 to 0.59 hr-1, the mean absorption time were between 0.73 to 0.89 hr, the volume of distribution ranged from 21.34 to 28.91 L and the elimination half-life varied between 1.23 to 1.34 hr.