Inhibition of hepatic drug metabolism by norethindrone

In order to assess the effect of norethindrone on hepatic drug metabolism in man, hepatic N-demethylation of aminopyrine was studied by means of the aminopyrine breath test (ABT) in 7 healthy women during two menstrual cycles. Aminopyrine metabolic clearance rates were also studied in 3 women. The women were examined at the ends of the first, second, and third weeks before starting progestogen therapy and at the same times during a second menstrual cycle during which they took norethindrone, 350 microgram/day. The ABT was 5.1 +/- 1.9% (mean +/- SD) during the three control weeks and lower (p less than 0.001) during the three weeks on norethindrone, 3.9 +/- 0.9%. Aminopyrine metabolic clearance rate also fell during norethindrone therapy. The data suggest that progestogens inhibit hepatic microsomal function.