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Spectral studies on the effect of a new steroidal anesthetic agent alphadione on rat hepatic microsomes.

Alphadione, a steroidal anesthetic formulation containing alphaxalone (3 alpha-hydroxy-5 alpha-pregnane-11, 20-dione) and alphadolone acetate (21-acetoxy-3 alpha-hydoroxy-5 alpha-pregnane-11, 20-dione) in polyoxyethylated castor oil (Cremophor EL) owes its short duration of action to rapid metabolic transformation rather than the redistribution into the body fat. Treatment of rats with alphadione (1 ml/kg; intraperitoneal route) induced an increase in the cytochrome P-450 content of the liver. The difference spectra were obtained only when alphadione or alphaxalone was added to the liver microsomal suspension while neither alphadolone acetate nor Cremophor EL induced any spectral changes. The spectral dissociation constant (Ks) for alphaxalone was 2.5 X 10(-3) mM suggesting that hydroxylation of alphaxalone is a cytochrome P-450 dependent reaction.