Clarithromycin bioequivalence study of two oral formulations in healthy human volunteers

Objective: To assess the bioequivalence of two tablet formulations of clari thromycin (Clamicin 500 mg from Medley Industria Farmaceutica, Brazil, as t he test formulation, and Biaxin 500 mg from Abbott Industries, USA, as the reference formulation). Methods: A single 500 mg oral dose of each formulat ion was administrated in 24 healthy volunteers of both sexes (12 males and 12 females). The study was conducted open, randomized, two-period crossover design with a 7-day interval between doses. The plasma concentrations of c larithromycin were quantified by reversed phase liquid chromatography coupl ed to tandem mass spectrometry (LC-MS-MS) with positive ion electrospray io nization using multiple reaction monitoring (MRM) method. 14-hydroxyclarith romycin concentration was estimated semiquantitatively as equivalent of cla rithromycin/ml. The precision of the method was evaluated using calibration curves and plasma quality control samples. The pharmacokinetic parameters calculated for both compounds included: AUC((0-48h)), AUC((0-)infinity()), C-max, C-max/AUC((0-48h)), T-max, T-1/2 and Ke. Results: Standard curves of clarithromycin in plasma were linear in the range of 0.05 mu g x ml(-1) to 10 mu g x ml(-1) (r > 0.999). The limit of quantification was 5 ng/ml. Wit hin- and between-run plasma quality control CV were 5.8% and 15.7%, respect ively. Inaccuracy within- and between-runs were 14% and 17%, respectively. 90% CI for clarithromycin geometric mean AUC((0-48h)), AUC((0-)infinity()) and C-max ratios (test/reference) were: 88.7% - 103.1%, 89.4% - 103.7% and 85.4% - 99.6%, respectively, and for hydroxyclarithomycin were 80.3% - 108. 6%, 80.1% - 110.1% and 85.4% - 112.6%, respectively. Conclusion: The method described for the quantification of charithomycin and its main metabolite is accurate and sensitive. Clamicin was considered bioequivalent to Biaxin based on the rate and extent of absorption. Since these were no significant differences in the bioequivalence determined using the pharmacokinetic par ameters of either clarithromycin or 14-hydroxyclarithromycin, we suggest th at future bioequivalence trials of this drug may be performed by quantifyin g clarithromycin only.