Effect of ethanol concentration on rates of ethanol elimination in normal and alcohol-treated rats in vivo.

Ethanol was infused intravenously to yield in the blood concentrations between 30 and 40 mM (low dose) or 80 and 90 mM (high dose). Duplicate blood samples were taken every 30 min for gas Chromatographie determination of ethanol. Elimination curves for both low and high does of ethanol were linear in normal rats until ethanol concentrations reached values of less than 5 mM. At the low and high doses, average rates of ethanol elimination were 179 ± l and 266 ± 13 μmoles/g/hr respectively. The stimulation of ethanol metabolism due to the high dose did not diminish as the concentration declined. At both doses in both normal and ethanol—pretreated rats, elimination rates were diminished over 80 per cent by prior treatment with 4-methylpyrazole. Pretreatment with aminotriazole produced a 20–25 per cent decrease in the rate at the high dose in normal rats and at both doses in ethanol-pretreated rats, but had no effect at the low dose in normal rats. From these data we conclude that a concentration effect of ethanol on rates of ethanol elimination, which has both an alcohol dehydrogenase—and a catalase-H₂O₂-dependent component, exists in vivo. Moreover, the adaptive increase in ethanol elimination due to chronic pretreatment with ethanol also involves both components. Pyruvate and ethanol pretreatment stimulated ethanol elimination at the low but not at the high dose of ethanol. It is further concluded that NADH reoxidation is rate-limiting for ethanol utilization at the low dose whereas the activity of alcohol dehydrogenase becomes limiting at the high dose and after pretreatment with ethanol in the fed state in vivo.