LACK OF INTERACTION BETWEEN 2 ANTIHISTAMINES, MIZOLASTINE AND CETIRIZINE, AND ETHANOL IN PSYCHOMOTOR AND DRIVING PERFORMANCE IN HEALTHY-SUBJECTS

The pharmacodynamic interaction between mizolastine, a new H-1 antihis tamine, and ethanol was assessed in a randomized, double-blind, three- way crossover, placebo-controlled study. Eighteen healthy young male v olunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo o nce daily for 7 days with a 1-week wash-out interval. An oral dose of ethanol or ethanol placebo, given 2 h after dosing on days 5 or 7 of e ach treatment period, was administered to achieve a peak blood alcohol concentration (BAG) of 0.7 g/1, then maintained for 1 h by two furthe r doses of ethanol. Driving ability and psychomotor performance were e valuated using actual and simulated driving tests, critical flicker fu sion threshold (CFF), adaptive tracking and divided attention (DAT) ta sks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in la teral deviation of 0.45 m, in braking reaction time of 80 ms, in drivi ng test and DAT performance of + 3.2; and a decrease in CFF and in tra cking speed of 2.6 m . s(-1). Neither mizolastine nor cetirizine signi ficantly impaired driving ability or arousal (CFF) compared with the p lacebo. However, both drugs significantly impaired DAT performance 6:0 0 h postdose (increase of + 2.1 for mizolastine and + 2.4 for cetirizi ne). The tracking speed was significantly 7:50 h after mizolastine adm inistration (-1.3 m . s(-1)) and more consistently from 1:30 to 7:50 h after cetirizine administration (-1.4 m . s(-1)). No significant adve rse interaction, i.e potentiation, occurred between ethanol and either antihistamine. No pharmacokinetic interaction occurred in BAG. In con clusion, treatment with a therapeutic dose of mizolastine or cetirizin e has minimal or no effect on human performance, does not impair drivi ng task performance and does not interact with ethanol at concentratio ns of 0.7 g .(-1).