EFFECT OF CHRONIC INTAKE OF ETHANOL ON PENTOBARBITAL METABOLISM

¹ Department of Pharmacology, University of Toronto, and Addiction Research Foundation of Ontario, Toronto, Canada

Intake of ethanol by rats, at a dose of 10 to 12 g/kg daily for two weeks, led to a slower onset and shorter duration of pentobarbital-induced sleep (30 mg/kg i.p.) than in pair-fed controls with isocaloric substitution of sucrose for ethanol. The pentobarbital concentrations in both plasma and brain were significantly lower in ethanol-treated animals at 15 minutes after injection, but not at 30 to 60 minutes. During the latter times, the rate of disappearance of pentobarbital from plasma did not differ in the two groups. The rate of metabolism of pentobarbital by liver slices in vitro was 33% lower for the chronic ethanol group than the controls. In contrast, pretreatment with phenobarbital for one week led to a significant increase in the rate of pentobarbital metabolism by liver slices. It is concluded that the changes in pentobarbital sleeping time after chronic ethanol treatment are primarily the result of changes in sensitivity of the nervous system, rather than of changes in distribution or metabolism of pentobarbital.