Bioequivalence study of cefepime intramuscular injection

Background: Cefepime, a fourth generation cephalosporin, is a broad spectrum antibiotic effective against both Gram positive and Gram negative bacteria. It is available from several pharmaceutical firms in southeast Asia. We studied bioequivalence of two products.

Objective: To assess the bioequivalence of two cefepime formulations: Cefamax 1 g intramuscular (Siam Pharmaceutical, Bangkok, Thailand) as the test formulation and Maxipime 1 g (Bristol-Myers Squibb, Bangkok, Thailand) as the reference formulation.

Methods: The study was conducted as an open, randomized, two-period crossover trial with a 1 week washout period in 18 healthy volunteers. Each subject received a single dose of 1 g intramuscular injection of the test or reference formulation. Blood samples were collected via an intravascular catheter at several time points over a 12 h period. Plasma cefepime concentrations were quantified by HPLC with photodiode array detection at 280 nm. The statistical comparisons for pharmacokinetic parameters were made using a paired t test.

Results: There was no significant difference in the logarithmically transformed values of C_max, AUC_0-12, and AUC_0-∞ between Cefamax and Maxipime using an analysis of variance (ANOVA). The 90% confidence intervals (CIs) of C_max, AUC_0-12, and AUC_0-∞ between the two formulations were 91.17-105.78, 90.29-97.63, and 88.89-96.57, respectively. All subjects had good tolerance and no serious adverse events were observed.

Conclusion: Cefamax 1 g intramuscular formulation is bioequivalent to Maxipime 1 g intramuscular formulation based on 90% CIs for C_max, AUC_0-12, and AUC_0-∞ within 80%-125%.