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 c onstant rate intravenous infusion (1.85 mg/min). The pharmacokinetics and pharmacodynamics of midazolam were determined following an intrave nous 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 pharmacologic al effect. Ethanol infusion resulted in a constant plasma alcohol conc entration 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 concentra tions was observed. These findings show that there is a pharmacodynami c interaction between midazolam and ethanol in vivo.