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Repeated-dose effects of mequitazine, cetirizine and dexchlorpheniramine on driving and psychomotor performance.

British journal of clinical pharmacology (2006-01-05)
Eef L Theunissen, Annemiek Vermeeren, Johannes G Ramaekers
RÉSUMÉ

Previous studies have demonstrated that the antihistamines mequitazine, cetirizine and dexchlorpheniramine produce mild sedation after single doses. It is unknown, however, whether acute sedation persists after repeated dosing. Therefore, this study assessed the effects of repeated dosing of these antihistamines on driving and psychomotor performance. Sixteen healthy volunteers were treated with mequitazine 10 mg q.a.m., cetirizine 10 mg q.a.m., dexchlorpheniramine Repetab 6 mg b.i.d. and placebo for four separate 8-day periods. Drug effects were assessed on days 1 and 8 using on-the-road driving tests (highway driving and car following), psychomotor tests (tracking and divided attention) and subjective questionnaires. Dexchlorpheniramine and mequitazine significantly impaired driving performance on the highway driving test on the first day; dexchlorpheniramine increased Standard Deviation of Lateral Position by 2 cm [95% confidence interval (CI) 0.5, 3.8] and mequitazine by 2.5 cm (CI 1.0, 4.3). These effects on driving performance disappeared after 8 days of treatment. No effect of treatment was found on car following, tracking and divided attention. Although subjective ratings confirmed that subjects knew their driving had been impaired in the mequitazine and dexchlorpheniramine condition after completion of the highway driving test on day 1, they did not expect their driving to be affected before the start of the test. Cetirizine did not impair performance on any of the tests. Single doses of mequitazine 10 mg and dexchlorpheniramine Repetab 6 mg cause mild driving impairment. However, when taken over several days, the impairing effect wears off, possibly as a result of tolerance.

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Sigma-Aldrich
(±)-Chlorpheniramine maleate salt, ≥99% (perchloric acid titration)
Supelco
Chlorpheniramine Maleate, Pharmaceutical Secondary Standard; Certified Reference Material
Sigma-Aldrich
S-(+)-Chlorpheniramine maleate salt
Supelco
Chlorpheniramine maleate salt solution, 1.0 mg/mL in methanol (as free base), ampule of 1 mL, certified reference material, Cerilliant®
Chlorphenamine maleate, European Pharmacopoeia (EP) Reference Standard
Dexchlorpheniramine maleate, European Pharmacopoeia (EP) Reference Standard