The pharmacokinetics of norethisterone have been studied in 8 women during and one month after treatment with rifampicin (450--600 mg/day). Rifampicin caused a significant reduction in the A.U.C. of a single dose of 1 mg norethisterone from 37.8 +/- 13.1 to 21.9 +/- 5.9 ng/ml X h (p less than 0.01). The plasma norethisterone half life (beta-phase) was also reduced from 6.2 +/- 1.7 to 3.2 +/- 1.0 h (p less than 0.0025). In one additional woman on long term oral contraceptive therapy the 12 hour plasma norethisterone concentration was reduced by rifampicin from 12.3 ng/ml to 2.3 ng/ml. Rifampicin caused a significant increase in antipyrine clearance, 6 beta-hydroxycortisol excretion and plasma gamma-glutamyltranspeptidase activity but there was no significant correlations between changes in these indices of liver microsomal enzyme induction. There was a significant correlation between the percentage increase in antipyrine clearance and the percentage decrease in norethisterone A.U.C. during rifampicin. The changes in norethisterone pharmacokinetics during rifampicin therapy are compatible with the known enzyme inducing effect of rifampicin.
PIP: The pharmacokinetics of norethisterone were studied in a group of women being treated with rifampicin during and after cessation of treatment with the rifampicin. The group of women was 9 patients receiving treatment of rifampicin for tuberculosis. 1 of the group was also receiving long-term contraceptive steroid therapy. Rifampicin caused a significant reduction in area under the plasma concentration (A.U.C.) and in the plasma norethisterone half life. Other changes in liver metabolism and urine excretion of hydroxy-corticosteroids were also exhibited. Such changes as appeared during the study are compatible with the known enzyme-inducing effect of rifampicin. Data from the study are tabulated and graphed. The study results show that rifampicin administration will cause a failure of oral contraceptive steroid therapy. This effect has previously been attributed to the kinetics of the estrogen component.