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Comparative kinetics and dynamics of zaleplon, zolpidem, and placebo
Author(s) -
Greenblatt David J.,
Harmatz Jerold S.,
Moltke Lisa L.,
Ehrenberg Bruce L.,
Harrel Lisa,
Corbett Kate,
Counihan Molly,
Graf Jennifer A.,
Darwish Mona,
Mertzanis Polyxane,
Martin Patrick T.,
Cevallos William H.,
Shader Richard I.
Publication year - 1998
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(98)90139-4
Subject(s) - zolpidem , hypnotic , pharmacology , crossover study , benzodiazepine , agonist , pharmacodynamics , placebo , digit symbol substitution test , chemistry , pharmacokinetics , anesthesia , medicine , receptor , insomnia , alternative medicine , pathology
Purpose This study evaluated the relationship of dose, plasma concentration, and time to the pharmaco‐dynamics of zaleplon and zolpidem, 2 structurally distinct benzodiazepine receptor agonists. Method Ten healthy male volunteers received single oral doses of placebo, 10 mg zaleplon, 20 mg zaleplon, 10 mg zolpidem, and 20 mg zolpidem in a double‐blind, 5‐condition crossover study, with 48 hours elapsing between trials. Plasma drug concentrations and pharmacodynamic effects were measured during the 8 to 24 hours after administration. Results Kinetics of zaleplon and zolpidem were not significantly related to dose. However, zaleplon had more rapid elimination (apparent elimination half‐life [t ½ ] of 1 hour) and higher apparent oral clearance (approximately 4300 mL/min) than zolpidem (t ½ , 2.0 to 2.2 hours; apparent oral clearance, 340 to 380 mL/min). Active treatments produced pharmacodynamic effects consistent with benzodiazepine agonist activity: self‐ and observer‐rated sedation, impairment of digit symbol substitution test (DSST) performance, impaired memory, and increased electroencephalographic activity in the beta frequency range. The overall order of agonist potency was as follows: placebo < 10 mg zaleplon < 20 mg zaleplon < 10 mg zolpidem < 20 mg zolpidem; on a number of measures, 20 mg zaleplon was comparable to 10 mg zolpidem. Quantitative effects of zolpidem 20 mg far exceeded those of other treatments. Dynamic effects of both drugs were significantly related to plasma concentration. Conclusions Benzodiazepine agonist effects of zaleplon and zolpidem were dose and concentration dependent. At the usual clinically effective hypnotic dose (10 mg of either drug), agonist effects of zolpidem exceeded those of zaleplon. Clinical Pharmacology & Therapeutics (1998) 64 , 553–561; doi: