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

Abstract

1 Oral contraceptives were shown to suppress the mid-cycle increase in methaqualone metabolism observed in premenopausal women not receiving oral contraceptive therapy. No women were identified in whom this suppression was not observed. 2 Combined oestrogen-progestogen contraceptives produced the effect in all nine women studied. The effect was also observed in one woman who was receiving progestogen-only contraceptives. 3 The effect of the combined contraceptives was observed within one month of the commencement of the contraceptive therapy. 4 The results emphasise the need to monitor the effect of the menstrual cycle in women not receiving oral contraceptive therapy when the effects of such therapy is studied. 5 These effects are more likely to be the consequence of an inhibition of hormonal control of hepatic metabolic activity by the synthetic steroids than they are to simple inhibition of hepatic metabolism.

PIP: In view of the authors' observation that the rate of methaqualone metabolism in healthy women is significantly increased at the time of ovulation, the effect of oral contraceptive (OC therapy) on methaqualone metabolism is studied. 9 women with no known pathological disorders, aged 21-35 who had been receiving 21 day combined OC therapy for a minimum of 6 months each received a 250 mg oral dose of methaqualone before retiring to bed on day 1 of bleeding and again 14 days later. A group of 9 women not receiving OC therapy received the drug on days 1 and 15 of a menstrual cycle and a group of 10 men received it once. The results of the study indicate that OCs of the combined estrogen-progestogen type abolish the mid menstrual cycle increase in the rate of methaqualone metabolism previously observed in healthy women. A similar result was obtained in 1 woman who had received progestogen-only therapy for 1 year but the significance of this result requires further study since progestogen-only OCs inhibit ovulation in only 15-40% of cycles. It was also found that OCs prolong the plasma half-life of drugs in women although the authors emphasize the need to monitor the time during a menstrual cycle when women not receiving OCs are studied. It has been observed that withdrawal of OC therapy after chronic administration in women resulted in a increased drug half-life. But this study supports the theory that a hormonally-mediated decrease in hepatic enzymic activity or hormonally-induced production of competing endogenous substrates were more likely mechanisms.