Bioequivalence of cefoperazone and sulbactam intramuscular injections commercially available in Thailand

Abstract

Bioequivalence of two products of 500/500 mg cefoperazone/sulbactam intramuscular injection commercially available in Thailand were studied. In vitro tests indicated that both products completely complied general specification requirements and they were pharmaceutical equivalence. Comparative bioavailability of a local product relative to an innovators product was conducted in 22 healthy Thai male volunteers. Each subject received a single dose of 500/500 mg cefoperazone/sulbactam injection intramuscularly in a randomized two way crossover design with 1 week washout period between dosing. Blood samples were collected at specified time intervals. Plasma was separated and analyzed for cefoperazone and sulbactam concentrations using a developed and validated HPLC method. The relevant pharmacokinetic parameters were determined from plasma concentration-time profiles of both products. The principal pharmacokinetic parameters (AUC[subscript 0-t], AUC[subscript 0-[infinity]] and C[subscript max]) were statistically evaluated based on log-transformed data for bioequivalence between the two products. The 90% confidence intervals for the ratios of log-transformed data of AUC[subscript 0-t], AUC[subscript 0-[infinity]] and C[subscript max] for cefoperazone and sulbactam of local product to that of innovators product were within 80-125%. Based on these statistical inferences, it was concluded that the two products were bioequivalence in terms of both the rate and extent of drug absorption into systemic circulation. In this study, the mean AUC 0-[infinity] values of cefoperazone and sulbactam were 166.16 +- 42.83 and 43.97 +- 10.42 microgram.hr/mL, respectively. The mean C[subscript max] values were 32.4 +- 7.0 and 18.57 +- 5.5 microgram/mL for cefoperazone and sulbactam, respectively. These values agreed with results of previous studies. However, the mean elimination half-life (t[subscript 1/2]) of cefoperazone (4.1 +- 1.6 hr) and sulbactam (1.5 +- 0.4 hr) appear tobe slightly greater