Comparative single-dose bioavailability study of two 500 mg clarithromycin tablet formulations in healthy volunteers under fasting condition

Abstract

Clarithromycin is a semi-synthetic macrolide antibiotic, chemically 6-0-methylerythromycin, formulated as immediate-release tablets, extended-release tablets, and granules for oral suspension. The objective of this study was to evaluate and compare the relative bioavailability, and therefore the bioequivalence of Clarithromycin 500 mg test formulation versus a reference Klacid® forte 500 mg formulation, following a single dose administration under fasting conditions. The study was a single center, open, single dose, randomized, two-way crossover study in healthy male volunteers, with a wash-out period of one week between study periods. Twenty-four male healthy volunteers, aged 18-49 years were included into study. Blood samples for determination of clarithromycin and 14-OH clarithromycin concentrations were withdrawn at zero (pre-drug administration), 0.33, 0.66, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24 and 36 hours post-drug administration. The determination of clarithromycin and 14-OH clarithromycin concentrations in plasma was performed using validated LC/MS/MS method and internal standardization after liquid/liquid extraction with methyl t-butyl ether. The test formulation of clarithromycin, dosed at 500 mg is bioequivalent for primary clarithromycin and 14-OH clarithromycin parameters (Cmax, AUC0-t and AUC0-∞) to the reference formulation after a single oral administration of 500 mg clarithromycin. Both medications were well tolerated with no serious adverse events. Thus, in view of the clinical use, both formulations are exchangeable without restrictions. Keywords: clarithromycin, 14-OH clarithromycin, bioavailability, bioequivalence study, single-dose