The in vivo metabolism of progestins. I. The metabolic clearance rates of progesterone and medroxyprogesterone acetate in the dog.

[3H]Medroxyprogesterone acetate (MPA) was synthesized by selective catalytic tritiation of the delta1-olefinic bond of 6alpha-methyl-17alpha-hydroxy-pregn-1,4-diene-3,20 dione acetate. [14C]MPA was synthesized by acetylation of 6alpha-methyl-17alpha-hydroxy-pregn-4-ene-3,20-dione with [14C]acetic anhydride. These radioactive materials were used to determine the MPA metabolic clearance rates (MCRMPA)and volumes of distribution (VoMPA) in dogs by the single injection technique. The metabolism of progesterone was also studied in the same animals. The MCRMPA (696 +/- 51 l/day) was only one-half that of progesterone (1332 +/- 59). By contrast, the volumes of distribution for the two steroids were similar. The metabolic clearance rates and the volumes of distribution for MPA and progesterone did not change during treatment with amino-glutethimide, a drug which is known to alter steroid metabolism in man.