URINARY AND BILIARY EXCRETION OF [4-14C]PROGESTERONE, [4-14C]20α- AND [4-14C]20β-HYDROXYPREGN-4-EN-3-ONE METABOLITES IN THE RABBIT

Abstract

SUMMARY [4-14C]Progesterone, [4-14C]20α- and 20β-hydroxypregn-4-en-3-one were injected intravenously into deeply anaesthetized rabbits and the bile and urine collected for 6 h. Neutral metabolites recovered after Ketodase hydrolysis of bile accounted for a mean of 82·8% (range 68·0–98·8%), 68·4% (61·0–80·0%) and 59·0% (57·0–61·0%) of the metabolites of progesterone, 20α-and20β-hydroxypregn-4-en-3-one, respectively. Acidic metabolites accounted for no more than 14·7% of the biliary radioactivity. Similar recoveries of neutral metabolites were obtained after hydrolysis of bile with 15% HCl, but only 41·0% (22·2–62·0%), 45·3% (36·4–55·4%) and 13·7% (10·6–16·9%) of the urinary metabolites were extractable as neutral metabolites. Acidic metabolites represented a further 33·9% (28·9–49·5%), 34·9% (27·5–40·4%) and 38·6% (29·4–47·8%) of the urinary radioactivity, respectively. Neutral ether soluble metabolites more polar than 5β-pregnane-3α,20α-diol were the most abundant metabolites. 3α-Hydroxy-5β-pregnan-20-one was identified in the bile as a metabolite of [4-14C]progesterone whereas 20α-hydroxypregn-4-en-3-one was present in the urine. 5β-Pregnane-3α, 20α-diol was identified as a biliary metabolite of [4-14C]20β-hydroxypregn-4-en-3-one.