Lack of effect of zafirlukast on the pharmacokinetics of azithromycin, clarithromycin, and 14-hydroxyclarithromycin in healthy volunteers

This randomized, open-label, crossover study,vas conducted to investigate w hether the coadministration of zafirlukast would affect the pharmacokinetic s of azithromycin, clarithromycin, or 14-hydroxyclarithromycin (14-OHC). Tw elve healthy subjects (six males and six females) received single 500-mg do ses of azithromycin and clarithromycin with and without zafirlukast given t o a steady-state concentration. Blood was collected prior to all macrolide doses and for 3 and 10 days after each clarithromycin and azithromycin dose , respectively. Serum was assayed for azithromycin, clarithromycin, and 14- OHC concentrations by validated high-performance liquid chromatography assa y systems. Data analyses were done by noncompartmental and nonparametric me thods. Analysis of the patients indicated that the addition of steady-state concentrations of zafirlukast did not significantly alter the pharmacokine tic parameters of or overall exposure (based on the area under the concentr ation-time curve) to azithromycin, clarithromycin, and 14-OHC, While zafirl ukast is a known inhibitor of CYP3A4, it does not appear to exert a clinica lly or statistically significant pharmacokinetic effect on azithromycin, cl arithromycin, or 14-OHC.