title: The pharmacokinetics and pharmacodynamics of zaleplon delivered as a thermally generated aerosol in a single breath to volunteers.
abstract: Pharmacokinetics, pharmacodynamics, safety, and tolerability of inhaled zaleplon were assessed in healthy volunteers. Forty participants received 0.5, 1, 2, or 4 mg zaleplon or placebo as a thermally generated aerosol in a randomized, double-blind, parallel-group, dose escalation study. Blood was collected up to 24 hours after dosing, and sedation was assessed up to 8 hours. Following inhalation, the observed median time to maximum plasma concentrations (25%, 75%) was 1.89 (1.45, 3.08) minutes and the mean (SD) elimination half-life was 1.24 (0.24) hours. The equilibration half-life for sedation (t(1/2) k(e0) ) was 1.16 (0.62, 2.17) minutes. The zaleplon AUC was dose proportional across doses, with a slope (90% confidence interval) of log-AUC versus log-dose of 0.92 (0.82, 1.02). No clinically significant changes were noted in laboratory values, vital signs, or spirometry. The most common adverse events were dizziness, somnolence, euphoria, headache, and visual disturbance. Zaleplon inhalation represents a safe, well-tolerated means of rapidly achieving effective plasma concentrations.
authors: Department of Anesthesiology and Mary Beth Donnelley Clinical Pharmacology Core Facility of the Robert H., Lurie Comprehensive Cancer Center of the Northwestern University Feinberg School of Medicine, Chicago, IL 60611-3008, USA. mja190@northwestern.edu
authors: Michael J
authors: MJ
authors: Avram
authors: Daniel A
authors: DA
authors: Spyker
authors: John H
authors: JH
authors: Kehne
authors: James V
authors: JV
authors: Cassella
mesh_terms: D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000336:Aerosols; D019540:Area Under Curve; D004311:Double-Blind Method; D005260:Female; D006207:Half-Life; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D000081:Acetamides; D000336:Aerosols; D006993:Hypnotics and Sedatives; D011743:Pyrimidines; C085665:zaleplon