Investigations of effects exerted by various compounds on hepatic microsomal mixed function oxidases are frequently designed for and performed under a single set of conditions with respect to dosage and time of sacrifice after drug administration. From these data a generalization may be derived as to whether a particular drug inhibits, induces or produces no change in these enzymes. Limitations of this approach are illustrated by experiments with GPA 1851, an imidazolone derivative with anti-inflammatory properties. Two hours after a single oral dose of 50 mg/kg, rat hepatic microsomal aniline hydroxylase and ethylmorphine N-demethylase activities were markedly reduced, whereas if the rats were sacrificed 24 h after this oral dose, aniline hydroxylase activity and cytochrome P-450 were enhanced. When rats were sacrificed 24 h after the last of 4 daily oral doses of GPA 1851, no significant change occurred in aniline hydroxylase or ethylmorphine N-demethylase activities, but cytochrome P-450 content was elevated.

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