Metabolic Fate of Orally Administered H3-Norethynodrel in Rabbits

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Abstract
The distribution of radioactivity in the urine, bile and feces of female rabbits following the oral administration of randomly tritiated 17α-ethynyl-17β-hydroxy- 5(10)-estrene-3-one has been measured. In 5 animals with bile drainage cannulae, 33 % of the administered radioactivity was excreted in the bile, 21% in the urine and 17% in the feces during 7 days. These results indicate that over 70% of the radioactivity was absorbed from the gut. In a control group of 3 normal and 2 sham-operated rabbits, 52% of the radioactivity was in the urine and 16 % in the feces, indicating that much of the activity in bile is reabsorbed and excreted in the urine. Less than 1 % of the radioactivity in bile was unconjugated, 81 % was conjugated as glucosiduronate and 18% as another conjugate, probably sulfate. Most of the glucosiduronate fraction was identified as 17α-ethynyl-3β,17β- dihydroxy-5(10)-estrene. In the urine, 1–2% of the radioactivity was unconjugated, 35–40% was glucosiduronate and 10–15% was sulfate. In the feces of cannulated and of control animals, 73 and 34%, respectively, of the radioactivity was extractable without hydrolysis. Much of the extractable activity in the feces was unchanged norethynodrel, while 3 other compounds were formed, namely, 17α-ethy nyl-17β-hy droxy- 19-norandrost- 4-ene-3-one, 17α-ethynyl-10β,17β-dihydroxy- 19-norandrost-4-ene-3-one and an unidentified ketone which probably lacked a side chain at C-17. Incubation with gastric juice and with blood led to partial conversion of norethynodrel to the same metabolites found in feces. It is concluded that part of the ingested norethynodrel was absorbed and reached the liver without prior change to other compounds.