Effects of Contraceptive Agents on Drug Metabolism in Various Animal Species

Abstract

I The effect on liver microsomal enzyme activity of three steroid contraceptive drug (SCD) combinations was compared in rats, mice and guinea-pigs. Lynestrenol plus mestranol, norethisterone plus mestranol and norethynodrel plus mestranol were given orally for 4 consecutive days (acute treatment) or 30 days (chronic treatment) at various doses eliciting an experimentally controlled antifertility activity which varied in its extent. 2 In rats and mice all the combined treatments (with the exception of norethynodrel plus mestranol in mice) were active as inducers of liver microsomal enzymes. This induction seems to be mediated mainly by the progestogenic compounds. Oestrogens showed a very poor effect bordering on significance only in a few cases. 3 No effect on liver microsomal protein or cytochrome P 450 concentration was obtained after treatment with doses capable of increasing the microsomal enzyme activity. 4 The activity of the liver microsomal enzymes did not appear to be reduced immediately (2 h) after the last administration of the SCD given during 4 or 30 days. 5Contraceptive treatments at doses capable of eliciting complete antifertility activity were inactive on liver microsomal enzyme activity in guinea-pigs.

Influence of sex and oral contraceptive steroids on paracetamol metabolism.

“…Again, the oestrogenic component of OCS appears to be responsible for the decreased elimination of these drugs (Chambers et al, 1982). Progestogens, in particular lynestrenol, increase the activity of a range of liver microsomal enzymes in rats and mice (Briatico et al, 1976), consistent with a selective effect of OCS on the various forms of cytochrome P-450. The oxidative metabolism of paracetamol is of major toxicological significance since it results in the formation of the reactive intermediate responsible for paracetamol-mediated hepatotoxicity.…”