ABSTRACTObjectivesTwo investigations aimed to define the pharmacokinetic profile of a modified‐release preparation of zaleplon (SKP‐1041).MethodsProtocol SOM001 was a 5‐way crossover, double‐blind, randomized trial comparing three novel modified‐release formulations of zaleplon 15 mg (SKP‐1041A, SKP‐1041B, SKP‐1041 C) to placebo and immediate‐release zaleplon 10 mg. Protocol SOM002 was a randomized, crossover, open‐label trial to compare the pharmacokinetics of SKP‐1041B after day and night administration. In SOM001, study drug was administered at 9:00 a.m. (fasted); blood samples were obtained beginning 1 h predose through 12 h postdose. In study SOM002, study drug was administered at 9:00 a.m. or 10:30 p.m.; blood samples were obtained beginning 1 h predose through 12 h postdose. Subjects were 19 (SOM001) and 23 (SOM002) healthy adults between ages 20–46.ResultsDose‐normalized total AUCs for modified‐release preparations A, B, C and immediate‐release zaleplon were not significantly different; peak plasma concentrations were similar for A and B, and both were significantly higher than C. Time to peak plasma concentration for A, B, and C were 4–5 h compared to 1.5 h for immediate‐release zaleplon; mean terminal phase half‐life was in the range 1–2 h for A, B and immediate‐release zaleplon. No significant differences were noted between day and night administration in the SOM002 study.ConclusionsZaleplon, 15 mg, in a novel, modified‐release formulation (SKP‐1041) had a time to peak plasma concentrations at 4–5 h postdose compared to 1.5 h for immediate‐release zaleplon, 10 mg. The pharmacokinetic profile suggests this formulation may be useful for treating middle‐of‐the‐night awakening. Copyright © 2011 John Wiley & Sons, Ltd.