ABSTRACT
OBJECTIVES: Two investigations aimed to define the pharmacokinetic profile of a modified-release preparation of zaleplon (SKP-1041). METHODS: Protocol 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-1041C) 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. RESULTS: Dose-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. CONCLUSIONS: Zaleplon, 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.