STEADY-STATE PHARMACOKINETICS AND ELECTROCARDIOGRAPHIC PHARMACODYNAMICS OF CLARITHROMYCIN AND LORATADINE AFTER INDIVIDUAL OR CONCOMITANT ADMINISTRATION

To evaluate the potential for an interaction between clarithromycin an d loratadine, healthy male volunteers (n = 24) received each of the fo llowing regimens according to a randomized crossover design: 500 mg of clarithromycin orally every 12 h (q12h) for 10 days, 10 mg of loratad ine orally q24h for 10 days, and the combination of clarithromycin and loratadine, A washout interval of 14 days separated regimens. The add ition of loratadine did not statistically significantly affect the ste ady-state pharmacokinetics of clarithromycin or its active metabolite, 14(R)-hydroxy-clarithromycin. However, the addition of clarithromycin statistically significantly altered the steady-state maximum observed plasma concentration and the area under the plasma concentration-time curve over a dosing interval for loratadine (+36 and +76%, respective ly) and for descarboethoxyloratadine (DCL), the active metabolite of l oratadine (+69 and +49%, respectively), Clarithromycin probably inhibi ts the oxidative metabolism of loratadine and DCL by the cytochrome P- 450 3A subfamily, Electrocardiograms (n = 12) were obtained over 24-h periods at baseline and steady state (day 10), The mean maximum QTc in terval and area under the QTc interval-time curve on day 10 were modes tly increased (<3%) from baseline for all three regimens, but no QTc i nterval exceeded 439 ms for any subject. Elevated steady-state concent rations of loratadine and DCL do not appear to be associated with adve rse cardiovascular effects related to prolongation of the QTc interval . Loratadine and clarithromycin were well tolerated, alone and in comb ination.