Biliary excretion of diethylstilbestrol in the rhesus monkey.

Abstract

The biliary excretion of diethylstilbestrol in the bile fistula rhesus monkey was investigated during exogenous taurocholate- and taurodehydrocholate-induced choleresis. Following intravenous administration, 36% of the dose was excreted into the bile (as diethylstilbestrol monoglucuronide) and 53% in the urine (as diethylstilbestrol monoglucuronide plus more polar unidentified metabolites). During the steady-state infusion of diethylstilbestrol, with taurocholate-induced choleresis, a bile flow dependent transport for the biliary excretion of diethylstilbestrol monoglucuronide was observed. Evidence for carrier-mediated transport of this metabolite was a bile-to-blood concentration ratio which ranged from 228 to 279 during steady-state experiments. In vitro experiments indicated that diethylstilbestrol monoglucuronide forms an association with taurocholate, as well as the micellar structures of bile, resulting in a severalfold enhancement of solubility above that in aqueous buffer alone. Taurodehydrocholate, a non-micelle-forming bile salt, did not interact with this metabolite and had no effect on its solubility. Substitution of taurodehydrocholate for taurocholate during the steady-state infusion of diethylstilbestrol produced no significant changes in the transport of diethylstilbestrol monoglucuronide from blood to bile.

• Authors: E J Mroszczak, S Riegelman
• Journal: Journal of pharmacokinetics and biopharmaceutics (J Pharmacokinet Biopharm) Vol. 6 Issue 4 Pg. 339-54 (Aug 1978) ISSN: 0090-466X [Print] United States
• PMID: 100590 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Taurocholic Acid
• Diethylstilbestrol

Topics

• Animals
• Bile (metabolism)
• Biliary Tract (metabolism)
• Biological Transport (drug effects)
• Diethylstilbestrol (metabolism)
• Haplorhini
• Macaca mulatta
• Male
• Taurocholic Acid (analogs & derivatives, pharmacology)