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.

Effects of thioridazine and diazepam on the pharmacokinetics of [14C]imipramine in rat: acute study.

The pharmacokinetics of [14C]imipramine (10 mg kg minus 1) were tested in male Wistar rats for interaction with thioridazine (16 mg kg minus 1) or diazepam (10 mg kg- minus 1). All drugs were administered orally with the test substances being given 40 min before [14C]imipramine dosing. Bile and urine were collected for 90 min after the radioactive drug was given. The animals were then killed and the tissues removed. Thioridazine reduced the excretion of radioactivity into the bile and urine, and increased the weight of the contents within the gastrointestinal tract. These effects were interpreted as being mainly due to a reduction in gastrointestinal motility resulting in a slower stomach emptying of [14C]imipramine. No effect on metabolism was detected. Diazepam pretreatment reduced the concentration ratio of radioactivity in the small intestinal contents to that of plasma, but did not alter the tissue distribution, metabolism or excretion of [14C]imipramine.

Effect of ethanol on toxicity and metabolism of amphetamine in the mouse.

Ethanol, 3 g/kg i.p., did not significantly alter the acute toxicity of amphetamine in the mouse. However, the urinary metabolite pattern was changed, suggesting that ethanol suppressed metabolism of the stimulant during the initial 6 h period. After 24 h, the mouse metabolized the same fraction of a given dose of amphetamine, whether it was given as amphetamine alone or amphetamine mixed with 2,3 or 4 g/kg ethanol.

The effect of salicylate on the biliary excretion of 14C-bishydroxycoumarin in rat.

1. The effect of intravenous sodium salicylate on the biliary excretion of 14C-bishydroxycoumarin ((14)C-BHC) was studied in rats.2. Salicylate (88.9 mg/kg) increased the biliary excretion of (14)C-radioactivity from a control value of 12.3 +/- 2.7% to 29.3 +/- 2.5% of the administered dose in 6 h after injection.3. During the 6 h period, 11% of the dose of radioactivity underwent biliary recycling in the salicylate-treated rats compared to only 6% in the absence of salicylate.4. About 15.3% of the radioactivity excreted in the bile of rats given BHC alone was detected as unchanged BHC, 8.6% was present as BHC-conjugate, conjugates of BHC metabolites accounted for 30.9%, and the remainder consisted of unidentified metabolites.5. Salicylate treatment did not significantly alter the excretory pattern of unchanged BHC and its metabolites.