Lack of interaction between two antihistamines,mizolastine and cetirizine,and ethanol in psychomotor and driving performance in healthy subjects

The pharmacodynamic interaction between mizolastine, a new H₁ antihistamine, and ethanol was assessed in a randomized, double-blind, three-way crossover, placebo-controlled study. Eighteen healthy young male volunteers received mizolastine 10 mg, or cetirizine 10 mg or placebo once 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 each treatment period, was administered to achieve a peak blood alcohol concentration (BAC) of 0.7 g/l, then maintained for 1 h by two further doses of ethanol. Driving ability and psychomotor performance were evaluated using actual and simulated driving tests, critical flicker fusion threshold (CFF), adaptive tracking and divided attention (DAT) tasks. Ethanol produced a significant decrement in all tasks up to 5.5 h after administration: an increase in steering movements of 4.6, in lateral deviation of 0.45 m, in braking reaction time of 80 ms, in driving test and DAT performance of +3.2; and a decrease in CFF and in tracking speed of 2.6 m·s^–1. Neither mizolastine nor cetirizine significantly impaired driving ability or arousal (CFF) compared with the placebo. However, both drugs significantly impaired DAT performance 6:00 h post-dose (increase of +2.1 for mizolastine and +2.4 for cetirizine). The tracking speed was significantly decreased 7:50 h after mizolastine administration (-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 adverse interaction, i.e potentiation, occurred between ethanol and either antihistamine. No pharmacokinetic interaction occurred in BAC. In conclusion, treatment with a therapeutic dose of mizolastine or cetirizine has minimal or no effect on human performance, does not impair driving task performance and does not interact with ethanol at concentrations of 0.7 g·^–1.