Lack of pharmacodynamic and pharmacokinetic interactions of the antihistamine ebastine with ethanol in healthy subjects

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Abstract
We have given 12 healthy subjects the H1-antihistamine ebastine (20 mg) or placebo in a double-blind, crossover study for one week each. The subjects were tested for drug effects on Day 6 of each period, and for interactions of ebastine with ethanol (0.8 g·kg−1) on Day 7. On both days, the testing runs were done at baseline and at 2, 4, and 6 h after the drug. Performance was evaluated both objectively (digit symbol substitution, flicker fusion, Maddox wing, nystagmus, simulated driving, body balance) and subjectively (visual analogue scales) and with questionnaires. Venous blood samples were taken daily during maintenance and during each test run for assay of plasma carebastine. Blood ethanol concentrations were assayed with an Alcolmeter in the breath and directly in the blood. Plasma carebastine concentration reached a steady-state from Day 3 on; the mean concentrations in the morning were 92 µg·l−1 on Day 6 and 104 µg·l−1 on Day 7. The rise in plasma carebastine after an extra 20 mg of ebastine was accelerated but not increased by ethanol. Ebastine did not impair performance objectively or subjectively. It slightly improved body balance and reduced errors during simple tracking at 4 h. Blood ethanol concentrations peaked (mean 0.76 g·l−1) at 1.5 h after ethanol intake. Ethanol impaired performance in most objective tests and produced clumsiness, muzziness, and mental slowness, but little drowsiness. Ebastine neither modified the blood ethanol concentrations nor increased the effects of ethanol. We conclude that treatment with 20 mg ebastine once daily for one week provides steady concentrations of carebastine in plasma without impairment of skilled performance or important interactions with alcohol.