Comparative bioavailability study of two cefixime formulations administered orally in healthy male volunteers

Abstract

The bioavatlabitity of a new cefixime ((6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-(carboxymethoxyimino) acetamido]-8oxo-3-vinyl-5-thia-1-azabicyclo-[4,2,0]-oct-2-ene-2-carboxylic acid, CAS 79350-37-1) tablet preparation (Loprax (R)) 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 AUCO-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, AUC(0-infinity) and AUC(0-24h) of cefixime were in the bioequivalence range (94%-112% Therefore, the two formulations were considered to be bioequivalent.