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Dissappearance of 1 alpha-3H-chlormadinone acetate from the plasma of women.


 The half-life and metabolic clearance rate of chlormadinone acetate were computed after a single iv injection of 60 to 90 mcCi 1-alpha-tritiated-chlormadinone acetate (specific activity 222 mcCi/mg) into 7 women aged 34-52 years. Plasma was extracted with acetone:MeOH for total radioactivity; then extracted with water and ether for free steroid radioactivity; then with n-butanol for conjugated steroid radioactivity; and finally extracted with chloroform:MeOH and chromatographed on thin layer with ether:benzene for specific radioactivity due to chlormadinone acetate. Blood samples were taken at .25, .5, 1, 8, 24 hours and every 24 hours for 5 days. The mean half-life of radioactivity specifically indentified as chlormadinone acetate for the first 24 hours was 2.6 hours, and after 24 hours was 81.8 hours, calculated by TAIT and BURSTEIN's method. All 4 curves, total radioactivity, conjugated steroids, free steroids, and specific activity had the same biphasic form: a rapid loss for about 24 hours, and an approaching equilibrium after 24 hours. The metabolic clearance rate was 42.61 liters per day, comparable to lynestrenol (15-30 liters) and norethynodrel. The half-life is much longer than that of progesterone (.96 and 10.7 minutes), estradiol (20 and 70 minutes), and norethynodrel (76 minutes and 45 hours). These data generate an estimate of the concentration of chlormadinone acetate in plasma of women taking .5 mg daily: about .45 ng/ml, i.e. about one-thirteenth the concentration of progesterone.
