Influence of ethinyloestradiol propanolsulphonate on serum bile acids in healthy volunteers.
The present work was done to clarify the relevance of altered serum bile acid (BA) profile in healthy women after the administration of the depot oestrogen ethinyloestradiol propanolsulphonate (EES). In the serum of 20 healthy women before and two times after oral EES application, 11 free and 14 taurine- and glycine-conjugated BA were analysed by HPLC with postcolumn derivatisation and fluorescence detection. EES significantly enhanced the total serum BA concentration and that of taurine-conjugated BAs, more pronounced the secondary BAs taurodeoxycholic, tauroursodeoxycholic and taurolithocholic acid. These secondary BAs are produced in the intestine by bacteria due to 7alpha-dehydroxylation of the primary BAs cholic and chenodeoxycholic acid. Because of unchanged free BAs, also produced by intestinal bacteria due to deconjugation, the results were interpreted as a sign of disturbed transport of BAs into the liver. Inhibition of the liver Na(+)-bile salt co-transporter (Ntcp) in the sinusoidal membrane by ethinyloestradiol, formed from the prodrug EES, may be responsible for the altered BA profile in serum.
Barth
Astrid
A
Institute of Pharmacology and Toxicology, Friedrich Schiller University Jena, Germany. Astrid.Barth@mti-n.uni-jena.de
Klinger
Gottwalt
G
Rost
Michael
M
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000097:blood*; D001692:Biological Transport; D002635:Chenodeoxycholic Acid / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D003277:Contraceptives, Oral, Combined / Q000493:pharmacokinetics*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004997:Ethinyl Estradiol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D005260:Female; D005998:Glycine / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D009640:Norethindrone / Q000493:pharmacokinetics*; D013654:Taurine / Q000378:metabolism
D001647:Bile Acids and Salts; D003277:Contraceptives, Oral, Combined; D004338:Drug Combinations; D002635:Chenodeoxycholic Acid; D013654:Taurine; D004997:Ethinyl Estradiol; C011436:Deposiston; D009640:Norethindrone; D005998:Glycine