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

Abstract

Preliminary experiments showed that measurable amounts of radioactivity appear in the bile of the rat shortly after oral administration of aqueous suspensions of isotopically labeled EE or EECPE. The observation that as much as 45% of the administered dose of EE and 27% of that of EECPE could be recovered from the 2s-hour bile samples indicated that the 2 compounds or their metabolites undergo an active enterohepatic circulation. It seemed, therefore, worthwhile to investigate the nature, distribution and biological activity of the radioactive substances appearing in the bile. The reabsorption of these substances was also studied.Materials and methods. A) The chromatographically pure compounds tested were ethynylstradiol-6,7 3H with a specific activity of 0.93 pc/pg and either ethynylestradiol-6,7 3H-3-cycl~pentyl ether with a specific activity of 0.78 pc/pg or a mixture of ethynylestradiol-6,7 3H-3-cyclopentyl ether with a specific activity of 0.78 pc/pg and ethynylestradiol-3-cy~lopentyl-l~~C ether with a specific activity of 0.0392 pc/pg. B) Rate of biliary excretion and preliminary characterization of biliary metabolites. Male albino rats, 350-400 g body weight, were used. Under ether anesthesia a polyethylene tubing (Intramedicm PE 10) was inserted into the common bile duct and secured in place by means of silk ligatures. TABLE I. Excretion of Radio-Metabolites of EECPE and EE in Rat Bile." Percentage of administered dose EECPE EE Time (hr) H3 c 7 4 H3 2% 27.0 19.8 45.5 5 37.4 22.0 58.0 * Three EECPE-treated rats per group; 2 EEtreated rats per group. Average bile volumes were : EECPE, 21/2 hr = 1.85 ml, 5 hr == 2.78 ml. EE, 2% hr 2.0 ml, 5 hr = 4.25 ml.

The effect of oral contraceptive steroids on bile secretion and bilirubin Tm in rats

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Drug Metabolism by Intestinal Microorganisms

“…However, the origin of the cecal 6-bromo-2-naphthyl-j3-glucosidase and -P-galactosidase activities was not determined. small extent following their infusion into the small intestine (50). Extensive enterohepatic circulation of diethylstilbestrol has been shown to take place in the rat (51).…”

Comparative Study of Ethynyloestradiol Metabolism in the Rabbit, Guinea Pig and Rat

“…The metabolism of ethynyloestradiol in rats has been extensively studied (5). Most of the radioactivity in plasma was present as a sulphate in that radioactivity could only be extracted after solvolysis.…”