Pharmacodynamic interaction between midazolam and a low dose of ethanol in vivo.
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.
Hoyo-Vadillo
C
C
Leiden/Amsterdam Center for Drug Research, University of Leiden, The Netherlands.
Mandema
J W
JW
Danhof
M
M
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004569:Electroencephalography; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D008874:Midazolam / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; D008874:Midazolam