Effect of ethanol on diazepam distribution in rat.

The effect of an acute oral dose of ethanol (3 g/kg), administered 30 min prior to oral administration of 14C-diazepam (5 mg/kg), on the fate of radioactivity in rats was examined. Ethanol pretreated rats possessed higher tissue levels at 60, 90 and 120 min than control animals. Blood, liver, kidney and plasma tissues showed 1.5 fold differences, adipose tissue exhibited a 2.4 to 3.6-fold increase, with brain showing 3.9, 4.5 and 5.4 fold higher levels of 14C at 60, 90 and 120 min respectively. Octanol extraction of plasma and ethyl acetate extraction of brain tissues indicated ethanol pretreated animals possessed a higher percentage of extractable radioactivity than controls. Thin-layer chromatography of the extracts suggested that biotransformation of 14C-diazepam was inhibited by ethanol, causing brain levels of 14C-diazepam at 60 min to be 6.4 fold higher than that observed in controls.