Abstract

The biological half-life (t/2) of hexobarbital measured by whole body analysis in CFW and ICR mice is 15 minutes. The t/2 in A/HeJ mice is 28 minutes. Analyses of mice at 1, 15 and 45 minutes after i.v. injection of 1 mg of hexobarbital indicate that the drug is convented to 2 major metabolites, 3-hythoxyhexobarbital and 3-ketohexobarbital. In vitro studies with the supernatant fraction of mouse liver containing the microsomes obtained after centnifugation at 9000 x g for 20 minutes show that 3-hydroxyhexobanbital and 3-ketohexobarbital account for most of the hexobarbital metabolized in all three strains of mice. Pretreatment of mice with phenobanbital, 80 mg/kg/day for four days, resulted in a 2-fold increase in the rate of formation of both these metabolites in vitro. The ratio of hydnoxyhexobarbital and ketohexobarbital was the same at 60 minutes in incubations of liver microsomes from control and pretreated mice. The identity of the metabolites has been established by countercurrent distribution, and mass spectroscopy with synthetic reference compounds.