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Electroencephalographic effects of benzodiazepines. II. Pharmacodynamic modeling of the electroencephalographic effects of midazolam and diazepam
Author(s) -
Bührer Michael,
Maitre Pierre O,
Crevoisier Charles,
Stanski Donald R
Publication year - 1990
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 - 10.1038/clpt.1990.192
Subject(s) - midazolam , diazepam , pharmacodynamics , hypnotic , anesthesia , pharmacokinetics , potency , pharmacology , medicine , chemistry , sedation , biochemistry , in vitro
The comparative pharmacodynamics of midazolam and diazepam were examined by use of the electroencephalogram as a measure of drug effect on the central nervous system. Intravenous doses of 7.5, 15, and 25 mg midazolam and 15, 30, and 50 mg diazepam were given on repeated occasions to three volunteers. Arterial plasma concentration and electroencephalogram voltage were related with nonparameteric and parametric pharmacodynamic models. The peak increases in voltage (maximal effect) and the slopes of the plasma concentration versus effect curve were similar for both drugs. The half‐time of blood:brain equilibration was significantly longer for midazolam than diazepam (4.8 minutes versus 1.6 minutes). Midazolam was found to have an intrinsic steady‐state potency that was approximately five times greater than that of diazepam (152 ng/ml versus 958 ng/ml). Clinical Pharmacology and Therapeutics (1990) 48, 555–567; doi: 10.1038/clpt.1990.192