ALTERATIONS IN KINETIC CONSTANTS FOR HEPATIC MICROSOMAL ANILINE HYDROXYLASE AND ETHYLMORPHINE N-DEMETHYLASE ASSOCIATED WITH PREGNANCY IN RATS

¹ Laboratories of Chemical Pharmacology, National Cancer Institute and National Heart Institute, National Institutes of Health, Bethesda, Maryland

Kinetic constants were determined for hepatic microsomal aniline hydroxylase and ethylmorphine N-demethylase in control female and pregnant rats for the following times after mating: 6 days, 20 days and about 23 days (1 day post partum). At none of these times did the _m values obtained in pregnant animals differ significantly from their respective nonpregnant controls. The V_max (per milligram of microsomal protein) for these enzyme activities did not differ between pregnant and nonpregnant animals on day 6 and 1 day post partum. However, for both metabolic reactions, the 20-day pregnant animals displayed significantly lower V_max values than controls. Changes in microsomal cytochrome P-450 content (per milligram of microsomal protein) paralleled the changes in enzyme activity, being significantly reduced in the 20-day pregnant animals but not different from controls at the other time periods. Hence, the lowered drugmetabolizing activity appears to parallel the change in cytochrome P-450 content.

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