The pharmacokinetics and pharmacodynamics of zaleplon delivered as a thermally generated aerosol in a single breath to volunteers

Michael J Avram*, Daniel A. Spyker, John H. Kehne, James V. Cassella

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

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 ke0 ) 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.

Original languageEnglish (US)
Pages (from-to)140-150
Number of pages11
JournalJournal of Clinical Pharmacology
Volume53
Issue number2
DOIs
StatePublished - Feb 1 2013

Keywords

  • Hypnotic
  • Inhalational delivery
  • Pharmacodynamics
  • Pharmacokinetics
  • Zaleplon

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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