Pharmacokinetic and bioequivalence of cefoperazone/sulbactam injection in healthy Thai volunteers

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Cheardchai Soontornpas
Chulaporn Limwattananon
Bungorn Sripanichkulchai
Thanee Thesiri
Piroon Mootsikapun

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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Research Articles
Author Biographies

Cheardchai Soontornpas, Faculty of Pharmaceutical Sciences, Khon Kaen University

Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

Chulaporn Limwattananon, Faculty of Pharmaceutical Sciences, Khon Kaen University

Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

Bungorn Sripanichkulchai, Center for Research and Development of Herbal Health Products. Faculty of Pharmaceutical Sciences, Khon Kaen University

Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

Thanee Thesiri, Faculty of Pharmaceutical Sciences, Khon Kaen University

Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.

Piroon Mootsikapun, Faculty of Medicine, Khon Kaen University

Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand

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