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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.

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In order to study the kinetics of norethindrone in women, we have administered single doses of 4 preparations of norethindrone (N) to Liverpool, England Department of Pharmacology and Therapeutics, University of LiverpoolNorethindrone ( 17a -ethinyl-I7 (3 -hydroxyestr-4-en-3-one) is a synthetic progestogen which is widely used both on its own and as a component of many combined contraceptive steroid preparations. Despite its widespread use, little is known of the relationship of blood concentrations of norethindrone to efficacy or toxicity. The plasma half-life (tV2) of norethindrone has been variously estimated as between 3 and 5 hrll and about 6 hr 9 , or as a biexponential decay with a terminal tV2 ranging between 3 and 12 hr. 6 We have developed a sensitive radioimmunoassay method for the measurement of norethindrone concentrations in plasma. 2During our initial studies in women taking the combined form of oral contraceptive, we found