Metabolism of alphaxalone in the rat: evidence for the limitation of the anaesthetic effect by the rate of degradation through the hepatic mixed function oxygenase system.

The rates of degradation of the steroid anaesthetic alphaxalone (3 alpha-OH-5 alpha pregnane-11,20 dione) have been studied in vitro using isolated hepatocyte and microsome preparations. Evidence is presented that alphaxalone is metabolized rapidly by the hepatic mixed function oxygenase system. Induction of cytochrome P450 in vivo leads to an increase in the maximum rate of degradation of alphaxalone in both in vitro systems. Induction of cytochrome P450 caused a decrease in the duration of the anaesthetic affect in vivo of a limiting dose of Althesin (alphaxalone/alphadolone acetate). It is concluded that, under certain conditions, the duration of the anaesthetic effect of alphaxalone is determined by the rate of metabolism of this compound by the mixed function oxygenase system of the liver.