A comparative clarithromycin bioavailability study: determination of clarithromycin and 14-(R)-hydroxyclarithromycin under fasting and fed conditions.
OBJECTIVE: To report the first comprehensive analysis of clarithromycin (CLA) and 14-(R)-hydroxyclarithromcin (14R) bioequivalence metrics under both fasting and fed conditions when using a validated analytical method. METHODS AND MATERIALS: In separate, single dose bioequivalence studies, fasting (n = 40) and fed (n = 18) non-smoking subjects entered a 2-treatment, 2-period, 2-sequence, crossover trial to assess the comparative bioavailability of a 500 mg generic clarithromycin tablet (IVAX Pharmaceuticals, NJ, USA) relative to the reference product (Biaxin Filmtab, Abbott Laboratories, IL, USA). The validated assay employed an HPLC coupled to a triple stage quadrupole mass spectrometer. RESULTS: The analytics permitted plasma samples to be measured for both analytes with high precision and a lower limit ofquantitation (LLOQ) of 11 ng/ml. In both fasting and fed studies, and for both analytes, the IVAX product met the common mean geometric ratio and 90% confidence limits in order to be declared bioequivalent with Biaxin Filmtab. Furthermore, the intra-subject variabilities for the comparative AUC metrics in both studies and for both analytes were < or = 21% and < or = 26% for Cmax. CONCLUSIONS: The fasting and fed results present definitive evidence that 500 mg IVAX clarithromycin and Biaxin Filmtab are bioequivalent under both fasting and fed conditions, whether based on CLA or 14R. Furthermore, at a 500 mg dose, clarithromycin is not a highly variable drug.