Comparative Bioavailability Study of Two Cefixime Formulations Administered Orally in Healthy Male Volunteers

Abstract

The bioavailability of a new Cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8-oxo-3-vinyl-5-thia-l-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax^®) was compared with that of a reference preparation of the drug in 24 healthy male volunteers. The trial was designed as an open, randomized, single-blind, two-sequence, two-period crossover study. Under fasting conditions, each subject received a single oral dose of 400 mg Cefixime tablet as a test or reference formulation on 2 treatment days. The treatment periods were separated by a one-week washout period. The plasma concentrations of the drug were analyzed by a rapid and sensitive HPLC method with UV detection. The pharmacokinetic parameters included AUC_0–24h, AUC_0–infinity, C_max, t_1/2, and K_e. The mean AUC0-infinity of Cefixime was 45008.7 ± 10989.9 and 45221.3 ± 2155.7 n · h/ml for the test and reference formulation, respectively. The maximum plasma concentration (C_max) of Cefixime was on average 4746.9 ± 1284 ng/ml for the test and 4726.3 ± 1206.9 ng/ml for the reference product. No statistical differences were observed for Cmax and the area under the plasma concentration-time curve for test and reference tablets. The calculated 90% confidence intervals based on the ANOVA analysis for the mean test/reference ratios of Cmax, AUC₀._intlnlty and AUC_0–24h of Cefixime were in the bioequivalence range (94%–l 12%). Therefore, the two formulations were considered to be bioequivalent.

Key words

Antibiotics, cephalosporin - CAS 79350-37-1 - Cefixime, bioavailability, bioequivalence - Loprax®

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