Abstract
Acute (4 days) and chronic (4 weeks) administration of methyltestosterone, cortisone and spironolactone changes drug metabolism in hepatic microsomes of male and female rats by altering the degree of binding of drugs to the cytochrome P-450, the activity of NADPH-cytochrome c reductase, and the rate of reduction of the cytochrome P-450-drug complex. These steroids also alter the ratio of stoichiometric relationship between drug metabolism and CO-inhibitable NADPH-oxidation. This ratio is sex dependent, being approximately 1·0 in males and 0·2 in females. The effect of the three steroids on the ratio is also sex dependent. The steroids tend to increase the ratio in females and decrease it in males.
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