Abstract
In the present study, the effects of coadministration of fexofenadine hydrochloride and erythromycin on the pharmacokinetics and electrocardiographic findings, focussed on QTc, were investigated. A double-blind, randomized, placebo-controlled, repeated-dose, orthogonal Latin square crossover study was conducted in 18 male healthy volunteers. Trial medication was given for three periods of 7 days separated by washout periods of 14 days. Fexofenadine hydrochloride (120 mg) was given twice a day for 7 days. Erythromycin (300 mg) was concomitantly given four times a day for 7 days.
During the administration of fexofenadine hydrochloride alone as well as during that of concomitant administration of fexofenadine hydrochloride and erythromycin, no problematic abnormality was observed in subjective/objective symptoms, blood pressure, pulse rate, body temperature or clinical laboratory findings.
The effect of concomitant administration on maximum plasma concentration at steady state (Cmax, ss), the steady-state area under the plasma concentration-time curve from 0 h to 12 h [AUCss (0-12)] and the apparent oral clearance from 0 h to 12 h at steady state [CLpo, ss (0-12)] was assessed comparing 90% confidence intervals with the range of 0.80-1.25 in accordance with EU and US FDA operating guidelines. When fexofenadine hydrochloride was coadministered with erythromycin, both mean Cmax, ss and mean AUCss (0-12) of fexofenadine were significantly higher than those for the administration of fexofenadine alone (p <0.05, respectively), while the mean CLpo, ss (0-12) of fexofenadine was significantly decreased (p <0.05). The change in plasma concentrations of erythromycin by the coadministration of fexofenadine hydrochloride, however, did not differ from that of the administration of erythromycin alone.
The QTc interval prolongation was evaluated as the difference between the mean values over 2 days before drug administration and the mean values over the 6th and 7th day after the administration. The QTc interval was not affected by the coadministration of fexofenadine and erythromycin. No significant periodical change in ECG parameters was noted.
These results indicate that neither the administration of fexofenadine hydrochloride alone nor the concomitant use of fexofenadine hydrochloride and erythromycin affects the ECG findings. It is also unlikely that concomitant use of fexofenadine hydrochloride and erythromycin results in clinical adverse events related to the cardiovascular system.
