Kinetics of norethindrone in women; II. Single‐dose kinetics

Abstract

In order to study the kinetics of norethindrone in women, we have administered single doses of 4 preparations of norethindrone (N) to 6 women (aged 21 to 23) in random order. The preparations were 1 mg N acetate and 50 µg ethinylestradiol EE 2 ) (Minovlar), a dose of 1.05 mg N (Noriday), 3 mg N acetate and 50 µg EE 2 (Gynovlar), and an intravenous preparation of 1 mg N with 50 µg EE 2 . Blood samples were taken at intervals up to 24 hr after dosing and plasma norethindrone concentrations were measured by radioimmunoassay. The plasma concentration decay slope fitted a two‐component open model with an initial rapid decay (half life 0.41 to 2.6 hr) followed by a slower beta phase with a half‐life of between 4.8 and 12.8 hr. The kinetics of norethindrone were not affected by the concomitant administration of EE 2 . The bioavailability of norethindrone after an oral dose of 1 mg was between 47% and 73% compared with an equivalent intravenous dose. The plasma clearance of norethindrone after 1 mg N acetate and 50 µg EE 2 was 404.7 ± 31.7 ml/kg/hr and the apparent volume of distribution was 4.28 ± 0.56 L/kg. These values were not significantly different from the figures obtained after administration of 1.05 mg N. After an oral dose of 3 mg N acetate and 50 µg EE 2 , the bioavailability of norethindrone was significantly less (between 32% and 70%) than that after 1 mg N acetate and 50 µg EE 2 explaining, at least in part, the lower than expected plasma concentrations of norethindrone in women on long‐term treatment with 3 mg N acetate and 50 µg EE 2 .