A Clinical Pharmacological Study to Evaluate the Sedative Effects of the Histamin H1 Antagonist, Diphenhydramine Hydrochloride (Drewell),in Healthy Male Elderly Subjects: Objective Evaluation of the Sedative Effects by Analysis of Saccadic Eye Movement

Drewell ® (diphenhydramine: DPH) is a histamine H1 receptor antagonist and the first OTC sleep aid in Japan. There are few studies which objectively evaluate the sedative effects in elderly subjects. The aim of present study was to evaluate the sedative effects of Drewell ® in healthy elderly and to compare the results with data from young subjects on which we reported previously.A placebo controlled, double-blind, crossover clinical pharmacological study was performed. Eight Japanese healthy elderly male volunteers received 2 tablets of Drewell ®, containing 50mg DPH, or matched placebo orally. Plasma levels of DPH after administration were measured hourly up to 4 hours and every 2 hours up to 8 hours. The sedative effects after the dose were measured by using the saccadic eye movement analyzing system for objective assessment and visual analogue scale (VAS) for subjective assessment.After Drewell ® administration the saccadic peak velocity (SPV) was decreased and saccade inaccuracy (IAC) was increased compared with placebo. There were no significant differences in saccade latency and VAS. The onset of significant decrease of SPV in elderly was delayed compared to young subjects (90 min in elderly vs 30 min in young) although pharmacokinetic parameters were similar in elderly and young subjects. However, the available data of both pharmacokinetic and pharmacodynamic at the same time point until sedation onset was only 60 min. Therefore further investigation is necessary to precisely determine the differences of onset of the sedative effect up to 90 min after Drewell ® administration.