title: Pharmacokinetic profile of SKP-1041, a modified release formulation of zaleplon.
abstract: OBJECTIVE
  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.
authors.affiliation: Program in Pharmacology and Experimental Therapeutics, Department of Molecular Physiology and Pharmacology, Tufts University School of Medicine and Tufts Medical Center, Boston, MA 02111, USA. dj.greenblatt@tufts.edu
authors.forename: David J
authors.initials: DJ
authors.lastname: Greenblatt
authors.forename: Jerold S
authors.initials: JS
authors.lastname: Harmatz
authors.forename: James K
authors.initials: JK
authors.lastname: Walsh
authors.forename: Rémy
authors.initials: R
authors.lastname: Luthringer
authors.forename: Luc
authors.initials: L
authors.lastname: Staner
authors.forename: Sarah
authors.initials: S
authors.lastname: Otmani
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Nedelec
authors.forename: Céline
authors.initials: C
authors.lastname: Francart
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Parent
authors.forename: Corinne
authors.initials: C
authors.lastname: Staner
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D000081:Acetamides / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D019540:Area Under Curve; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D018757:GABA Modulators / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics
chemical_list: D000081:Acetamides; D003692:Delayed-Action Preparations; D018757:GABA Modulators; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; C085665:zaleplon