Gastrointestinal metabolism of contraceptive steroids.
A number of oral contraceptive steroids undergo first-pass metabolism in the gastrointestinal mucosa. Ethinyl estradiol (mean systemic bioavailability 40% to 50%) is extensively metabolized, principally to a sulfate conjugate. In vivo studies that use portal vein catheterization and the administration of radiolabeled ethinyl estradiol have shown that the fraction of steroid metabolized in the gut wall is 0.44. In vitro studies with jejunal biopsy samples or larger pieces of jejunum or terminal ileum mounted in Ussing chambers have indicated that more than 30% of added ethinyl estradiol is sulfated. The progestogen desogestrel is a prodrug that is converted to the active metabolite 3-ketodesogestrel. Substantial first-pass metabolism of desogestrel occurs in the gut mucosa, with evidence from Ussing chamber studies for the formation of the active metabolite. Another progestogen, norgestimate, is also metabolized by the gut wall in vitro of which the principal metabolite is the deacetylated product, norgestrel oxime. It seems very likely that this will also occur in vivo. Drug interactions occurring in the gut wall have been reported with ascorbic acid (vitamin C) and paracetamol.
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D J
DJ
Department of Pharmacology and Therapeutics, University of Liverpool, England.
Madden
S
S
Orme
M L
ML
D000368:Aged; D001682:Biological Availability; D003278:Contraceptives, Oral, Hormonal / Q000378:metabolism* / Q000493:pharmacokinetics; D017135:Desogestrel; D004997:Ethinyl Estradiol / Q000378:metabolism / Q000493:pharmacokinetics; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009644:Norgestrel / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D009652:Norpregnenes / Q000378:metabolism / Q000493:pharmacokinetics; D013431:Sulfates / Q000378:metabolism
D003278:Contraceptives, Oral, Hormonal; D009652:Norpregnenes; D013431:Sulfates; D009644:Norgestrel; D004997:Ethinyl Estradiol; D017135:Desogestrel; C017576:norgestimate