Studies on Biliary Metabolites of Orally Administered Ethynylestradiol (EE) and its 3-Cyclopentyl Ether (EECPE-Quinestrol)

Abstract

Large amounts of radioactivity appeared in the bile at 21/2 and 5 hours after a single oral dose of radiolabeled EECPE or EE. Conjugated metabolites (glucuronides and sulfates) predominated in bile although their pattern of distribution differed markedly from that observed in plasma of the same rats. Intestinal washings obtained from treated rats with bile duct cannulas suggested that some alteration of both EECPE and EE may occur in the gut. Thin layer chromatograms of extracts of bile obtained from EE- or EECPE-treated rats did not reveal the presence of unaltered EE or EECPE. However, several of the TLC fractions exerted uterotrophic activity when administered orally to immature rats. The dose response curves were similar to those of EE, suggesting loss of lipophilic properties in the case of EECPE metabolites. None of the fractions were as potent as EE or EECPE. When bile from EECPE-treated donor rats was infused into the small intestine of recipient rats, radioactivity appeared in the plasma and bile of the recipients providing direct evidence of active enterohepatic circulation of metabolites. Little or no radioactivity accumulated in body fat confirming the loss of lipophilic properties following biliary cycling.