Objective

The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM‐1 after administration of a single oral dose to healthy volunteers in a placebo‐controlled double‐blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM‐1 were also investigated.

Methods

Males and females 18–45 years of age received SM‐1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography.

Results

Similar number and severity of adverse events were observed following administration of SM‐1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5–1 hr postdose, lasting about 7–7.5 hr. Plasma concentration curves for the two delayed‐release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually.