Effect of oral contraceptives on drug metabolism

Abstract

The effects of chronic steroid contraceptive use on drug‐metabolizing activity were studied by using plasma antipyrine (ap) and phenylbutazone (pbz) half‐lives in women and in vitro N‐demethylation of O‐ethylmorphine by female rat liver preparations. After 3 months of oral steroid therapy (norethynodrel plus mestranol), the antipyrine half‐life was increased in 5 of 8 sub;ects (as compared to their previous half‐lives), whereas the pbz half‐life was not COnsistently altered. After chronic injections of norethynodrel‐mestranol (200 p.g per rat per day plus 4 p.g per rat per day, respectively) for 10 days or 6 weeks, ethylmorphine demethylation by rat livers was significantly increased. A higher dose of norethynodrel‐mestranol but not a lower dose also stimulated ethylmorphine demethylation activity. The acute addition of norethynodrel or mestranol in vitro competitively inhibited ethylmorphine demethylation. Under the conditions of the observations, therefore, the rat cannot be used as a model for the effects of the chronic use of oral steroid contraceptives in women.