DIAZEPAM EFFECTS ON THE PERFORMANCE OF HEALTHY-SUBJECTS ARE NOT ENHANCED BY TREATMENT WITH THE ANTIHISTAMINE EBASTINE

1 We have given 12 healthy subjects the H-1-antihistamine ebastine (20 mg) or placebo in a randomized double-blind and crossover study for 1 week each. The subjects were tested for drug effects on day 6 of each period, and for interactions of ebastine with oral 15 mg diazepam (DZ) on day 7. On both days, the testing runs were at baseline and 1.5, 3, 4.5 and 6 h after intake. 2 The performance was evaluated both objectively (digit symbol substitution, flicker fusion, Maddox wing, simulated driving, body balance) and subjectively (visual analogue scales, questionnaires). Venous blood was sampled daily during the maintenance and during each testing round for the assay of plasma carebastine (the active metabolite of ebastine) by high pressure liquid chromatography and plasma diazepam by radioreceptor assay. Three-way ANOVA, paired t-test, Wilcoxon rank sign test and Fisher's fourfold table test were used for data analysis. 3 Plasma carebastine reached steady levels from day 3 onwards. The mean concentrations in the morning were 82 mug l-1 on day 6 and 85 mug l-1 on day 7. The rise (+ 150%) in plasma carebastine after an extra 20 mg ebastine was not modified by DZ. Ebastine did not affect performance objectively or subjectively, yet borderline drowsiness was recorded during the first 3 h. On day 7, plasma DZ concentrations peaked (mean 480 mug l-1) at 1.5 h after the intake. DZ produced impaired performance in various objective tests, and drowsiness, weakness, clumsiness, mental slowness and poor performance were reported on visual analogue scales. Ebastine neither modified plasma DZ concentrations nor increased DZ effects. 4 We conclude that treatment with 20 mg ebastine once daily for 1 week provides steady concentrations of carebastine in plasma, without impairment of skilled performance or important interactions with diazepam.