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 in;ections 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.

The influence of oral contraceptives on the metabolism of methaqualone in man.

“…Several groups of workers have shown that oral contraceptive steroids prolong the plasma half-life of drugs in women (O'Malley et al, 1972;Carter et al, 1973;Herz etal., 1978;Homedia etal., 1978;Roberts et al, 1979;Abernathy & Greenblatt 1981). Our results are consistent with their findings but emphasise the need to monitor the time during a menstrual cycle when women not receiving contraceptive therapy are studied.…”

“…This increase in antipyrine serum halflife confirmed earlier findings of O'Malley et al (1972) and is in agreement with similar findings for aminopyrine observed by Herz et al (1978). The work of O'Malley et al (1972) andCarter et al (1973) however indicated that not all drugs were equally sensitive to oral contraceptive therapy as both groups observed no statistically significant increase in the half-life of phenylbutazone. The results of Carter et al (1973) also indicated that hepatic metabolic activity in women may vary in its sensitivity to oral contraceptives as they observed a significant increase in the serum half-life of antipyrine in only five out of eight subjects after three months therapy.…”

Effects of tobacco smoking and oral contraceptive use on theophylline disposition.

“…Many oxidative pathways such as for antipyrine (Carter et al, 1974;Teunissen et al, 1982), and theophylline (Tornatore et al, 1982) and reductive processes such as for nitrazepam (Jochemsen et al, 1982) exhibit decreased metabolism rates. On the other hand, the conjugation of lorazepam and oxazepam is increased in OC users (Patwardhan et al, 1981).…”

Antipyrine elimination in saliva after low‐dose combined or progestogen‐ only oral contraceptive steroids.

“…Some of these investigations have utilised OCS preparations containing both oestrogens and progestogens (combined preparations) which have had a high oestrogen content (highdose preparations) (O'Malley et al, 1970(O'Malley et al, , 1972Carter et al, 1974Carter et al, , 1975. Only two investigations (Homeida et al, 1978;Abernethy & Greenblatt, 1981) have used currently preferred low-dose OCS preparations (50 ,ug oestrogen or less).…”