Abstract
1. We have given 12 healthy subjects the H1-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 micrograms l-1 on day 6 and 85 micrograms 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 micrograms 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.(ABSTRACT TRUNCATED AT 250 WORDS)
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- Fisch H. U., Groner M., Groner R., Menz C. Influence of diazepam and methylphenidate on identification of rapidly presented letter strings: diazepam enhances visual masking. Psychopharmacology (Berl) 1983;80(1):61–66. doi: 10.1007/BF00427497. [DOI] [PubMed] [Google Scholar]
- Hannington-Kiff J. G. Measurement of recovery from outpatient general anaesthesia with a simple ocular test. Br Med J. 1970 Jul 18;3(5715):132–135. doi: 10.1136/bmj.3.5715.132. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Linnavuo M., Yliläkkölä P., Mattila M. J., Mäki M., Seppälä T. A new device to measure drug-induced changes on reactive and coordinative skills of human performance. Pharmacol Toxicol. 1987 Aug;61(2):142–147. doi: 10.1111/j.1600-0773.1987.tb01792.x. [DOI] [PubMed] [Google Scholar]
- Mattila M. J., Kuitunen T., Plétan Y. Lack of pharmacodynamic and pharmacokinetic interactions of the antihistamine ebastine with ethanol in healthy subjects. Eur J Clin Pharmacol. 1992;43(2):179–184. doi: 10.1007/BF01740667. [DOI] [PubMed] [Google Scholar]
- Mattila M. Acute and subacute effects of diazepam on human performance: comparison of plain tablet and controlled release capsule. Pharmacol Toxicol. 1988 Nov;63(5):369–374. doi: 10.1111/j.1600-0773.1988.tb00970.x. [DOI] [PubMed] [Google Scholar]
- Mattila M., Mattila M. J., Vrijmoed-de Vries M., Kuitunen T. Actions and interactions of psychotropic drugs on human performance and mood: single doses of ORG 3770, amitriptyline, and diazepam. Pharmacol Toxicol. 1989 Aug;65(2):81–88. doi: 10.1111/j.1600-0773.1989.tb01132.x. [DOI] [PubMed] [Google Scholar]
- Moser L., Hüther K. J., Koch-Weser J., Lundt P. V. Effects of terfenadine and diphenhydramine alone or in combination with diazepam or alcohol on psychomotor performance and subjective feelings. Eur J Clin Pharmacol. 1978 Dec 18;14(6):417–423. doi: 10.1007/BF00716383. [DOI] [PubMed] [Google Scholar]
- Savolainen K., Linnavuo M. Effects of m-xylene on human equilibrium measured with a quantitative method. Acta Pharmacol Toxicol (Copenh) 1979 Apr;44(4):315–318. doi: 10.1111/j.1600-0773.1979.tb02336.x. [DOI] [PubMed] [Google Scholar]
- Vincent J., Liminana R., Meredith P. A., Reid J. L. The pharmacokinetics, antihistamine and concentration-effect relationship of ebastine in healthy subjects. Br J Clin Pharmacol. 1988 Nov;26(5):497–502. doi: 10.1111/j.1365-2125.1988.tb05288.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vincent J., Sumner D. J., Reid J. L. Ebastine: the effect of a new antihistamine on psychomotor performance and autonomic responses in healthy subjects. Br J Clin Pharmacol. 1988 Nov;26(5):503–508. doi: 10.1111/j.1365-2125.1988.tb05289.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wood-Baker R., Holgate S. T. Dose-response relationship of the H1-histamine antagonist, ebastine, against histamine and methacholine-induced bronchoconstriction in patients with asthma. Agents Actions. 1990 Apr;30(1-2):284–286. doi: 10.1007/BF01969062. [DOI] [PubMed] [Google Scholar]