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Zaleplon pharmacokinetics and absolute bioavailability
Author(s) -
Rosen Amy S.,
Fournié Philippe,
Darwish Mona,
Danjou Philippe,
Troy Steven M.
Publication year - 1999
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/(sici)1099-081x(199904)20:3<171::aid-bdd169>3.0.co;2-k
Subject(s) - pharmacokinetics , bioavailability , crossover study , hypnotic , volume of distribution , oral administration , pharmacology , medicine , half life , anesthesia , alternative medicine , pathology , placebo
The pharmacokinetics and absolute oral bioavailability of zaleplon were assessed to evaluate the extent of presystemic metabolism of this new nonbenzodiazepine hypnotic agent. A partially randomized, single‐dose, four‐period crossover study was conducted in 23 healthy subjects. Subjects received 1 and 2.5 mg intravenous (iv) infusions of zaleplon during the first and second periods, respectively, and then were randomly assigned to receive a 5 mg oral dose or 5 mg iv infusion of zaleplon in a crossover design during the final two periods. Zaleplon pharmacokinetics were determined in 20 subjects (ten men and ten women) after the two 5 mg treatments. The oral and iv doses of zaleplon administered in this study were safe and well‐tolerated. Following iv administration, zaleplon had a moderate to high systemic clearance (mean±S.D., 0.94±0.20 L/h/kg), rapid elimination (half‐life, t 1/2 =1.05±0.13 h), and a steady‐state volume of distribution of 1.27±0.25 L/kg, indicating substantial distribution into extravascular tissues. Zaleplon was rapidly absorbed after oral administration, and the mean apparent elimination t 1/2 was similar to that obtained after iv infusion. The absolute bioavailability was 30.6±10.2%. Copyright © 1999 John Wiley & Sons, Ltd.