Pharmacodynamic interaction between midazolam and a low dose of ethanol in vivo

Publication Type:

Journal Article

Authors:

Hoyo-Vadillo, C.; Mandema, J.W.; Danhof, M.

Source:

Life Sci, Volume 57, Number 4, p.325-33 (1995)

ISBN:

0024-3205 (Print)

DOI Name (links to online publication)

Keywords:

Animals; Dose-Response Relationship; Drug; Drug Interactions; Electroencephalography; Ethanol/*pharmacology; Male; Midazolam/*pharmacokinetics/pharmacology; Rats; Rats; Wistar

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/l (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.