Pharmacokinetic and bioequivalence of cefoperazone/sulbactam injection in healthy Thai volunteers
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Abstract
Introduction : Bioequivalence study of a generic drug is a registration requirement regulated by the Thai Food and Drug Administration. The present study was performed to assess the bioequivalence of a generic formulation of cefoperazone/sulbactam (1.0/0.5 g) compared with an innovator’s formulation both by intramuscular injection. Material and method : A single dose, two period, two sequence, double blind, randomized cross-over with a one-week washout period was used. Twenty healthy Thai volunteers were recruited into the present study. All subjects were intramuscularly injected with a single dose of cefoperazone/sulbactam (1.0/0.5 g). Blood samples were collected before injection and at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10 and 12 hours after injection. Plasma concentrations of cefoperazone and sulbactam were assayed by a validated HPLC method. The pharmacokinetic parameters were calculated using a non-compartmental model and Wilcoxon Signed Rank test and ANOVA were used for statistical testing. Results : Time to reach the peak concentration of cefoperazone and sulbactam in all volunteers who were injected with either generic or innovator’s product were not signifcantly different (p > 0.05). Maximum concentration, area under the concentration time curve from time 0 to time t and area under the concentration time curve from time 0 to time infnity of cefoperazone/sulbactam were 61.9 ± 20.3/25.5 ± 10.4 μg/mL, 247.4 ± 63.7/64.2 ± 21.3 μg.h/mL and 264.8 ± 64.7/69.2 ± 24.1 μg.h/mL, respectively, for the generic product and 59.4 ± 17.7/25.5 ± 8.0 μg/mL, 245.0 ± 66.5/65.3 ± 22.4 μg.h/mL and 258.8 ± 67.4/70.6 ± 24.8 μg.h/mL, respectively for the innovator’s product. Conclusion : The generic and innovator’s product of cefoperazone/sulbactam (1.0/0.5 g) injections used in the present study were bioequivalent. The 90% confdence intervals of the log transformed data of ratio of Cmax, AUC0-12h or AUC0-∞ between generic and innovator’s product, both cefoperazone and sulbactam, were within the bioequivalence range of 0.80-1.25. Other pharmacokinetic parameters of both products were not signifcantly different.
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