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Pharmacodynamic interaction between midazolam and a low dose of ethanolin vivo

Authors
Journal
Life Sciences
0024-3205
Publisher
Elsevier
Publication Date
Volume
57
Issue
4
Identifiers
DOI: 10.1016/0024-3205(95)00291-d
Keywords
  • Ethanol
  • Midazolam
  • Pharmacodynamic Interactions
Disciplines
  • Biology
  • Pharmacology

Abstract

Abstract The pharmacokinetic and pharmacodynamic interactions between midazolam and ethanol were studied in the rat in vivo. Ethanol was given as a constant rate intravenous infusion (1.85 mg/min). The pharmacokinetics and pharmacodynamics of midazolam were determined following an intravenous dose of 5 mg/kg in 15 minutes. Amplitudes in the 11.5–30 Hz (beta) frequency band of the EEG was used as a measure of the pharmacological effect. Ethanol infusion resulted in a constant plasma alcohol concentration of 0.44 ± 0.04 g/1 (Mean ± SE) and had no effect on the baseline value of the EEG effect parameter. Also the pharmacokinetics of midazolam were unchanged. However, a significant parallel shift of the midazolam concentration-EEG effect relationship to lower concentrations was observed. These findings show that there is a pharmacodynamic interaction between midazolam and ethanol in vivo.

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