Azithromycin Tablets In Healthy Relative Bioavailability And Bioequivalence Of Test

Bioavailability is a crucial indicator to ensure the quality of drug while bioequivalence serves as an important base on which the quality of different preparations within the same drug are ensured to be identical. The basis of this study is to develop a sensitive and specific analytical method for the determination of azithromycin in human biological samples. One microbiological assay method (Cylinder-plate method) for the determination of azithromycin in human plasma was developed and validated and was used in the relative bioavailability and bioequivalence study of azithromycin.A sensitive and specific, microbiological assay has been developed and validated for the determination of azithromycin in human plasma. The assay was reproducible and linear for azithromycin in the range of 0.0048～0.8546μg/ml. The lower limit of quantification of azithromycin was 0.0048μg/ml. The intra-day and inter-day precision (expressed as RSD%) was less or equal to 15% and accuracy (added quantities recovery) was within 85%～115%.The single oral dose relative bioavailability and bioequivalence study of two bands of azithromycin tablets was studied in healthy male volunteers by the above validated microbiological assay.A single oral dose of 500 mg of test preparation and reference preparation of azithromycin was administered to 19 healthy man volunteers, respectively, in a randomized, two-period cross-over design. The washout period was two weeks.After dosing, serial blood samples were collected for a period of 144 h. Plasma concentrations of azithromycin were analyzed using microbiological assay. Pharmacokinetic parameters including AUC0-24h, AUCo, Cmax, tmax, and t1/2 were determined.The results showed that t1/2 were 34.61±7.419h and 31.16±5.28h, Cmax were 557.15±12957μg/L and 548.34±137.61μg/L, tmax were 2.605±0.209 h and 2.550±0.16 h, AUC0-24h were 8452.1±2286.1μg-h/L and 8665.0±2343.7μg·h/L, AUCo were 8860.6±2359.8μg.h/L and 9009.5+±492.2μg·h/L following oral administration of test and reference preparation, respectively. The relative bioavailability and bioequivalence of AUCo-24h was 99.0±20.4%, the relative bioavailability and bioequivalence of AUCo was 100.0±19.0%.AUCo-24hand Cmaxwere tested for bioequivalence after log-transformation of data. No significant difference was found based on analysis of variance and two one side t-test of significance. 90% confidence intervals for test preparation / reference preparation ratios of AUCo-24h were found within the bioequivalence acceptance range of 80-125%. 90% confidence intervals for test preparation / reference preparation ratios of Cmax were found within the bioequivalence acceptance range of 70-143%. Based on the above statistical results, it was concluded that the test preparation is bioequivalent to the reference preparation.