Factors affecting the enterohepatic circulation of oral contraceptive steroids

https://doi.org/10.1016/0002-9378(90)90555-LGet rights and content

Abstract

Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled stuides have not confirmed this observation. Although gut flora are altered by oral antibotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol.

References (51)

  • DJ Back et al.

    Reduction of the enterohepatic circulation of norethisterone by antibiotics in the rat. Correlation with changes in the gut flora

    J Steroid Biochem

    (1980)
  • DJ Back et al.

    The effect of rifampicin on the pharmacokinetics of ethynylestradiol in women

    Contraception

    (1980)
  • DJ Back et al.

    The interaction of phenobarbital and other anticonvulsants with oral contraceptive steroid therapy

    Contraception

    (1980)
  • DJ Back et al.

    Pharmacokinetics of oral contraceptive steroids following the administration of the antimalarial drugs primaquine and chloroquine

    Contraception

    (1984)
  • JV Joshi et al.

    A study of interaction of low dose combination oral contraceptive with ampicillin and metronidazole

    Contraception

    (1980)
  • SFM Grimmer et al.

    The effect of cotrimoxazole on oral contraceptive steroids in women

    Contraception

    (1983)
  • RJ Warren et al.

    Radioimmunoassay of ethynylestradiol

    J Endocrinol

    (1974)
  • MLE Orme et al.

    Clinical pharmacokinetics of oral contraceptive steroids

    Clin Pharmacokinet

    (1983)
  • DJ Back et al.

    The gut wall metabolism of ethynylestradiol and its contribution to the pre-systemic metabolism of ethynylestradiol in humans

    Br J Clin Pharmacol

    (1982)
  • HM Bolt et al.

    Pharmacokinetics of mestranol in man in relation to its oestrogenic activity

    Eur J Clin Pharmacol

    (1974)
  • DJ Back et al.

    Pharmacokinetics of norethindrone in women. (2) Single dose pharmacokinetics

    Clin Pharmacol Ther

    (1978)
  • SF Sisenwine et al.

    Urinary metabolites of D L-norgestrel in women

    Acta Endocrinol

    (1973)
  • DJ Back et al.

    Drug metabolism by gastrointestinal mucosa-clinical aspects

  • DJ Back et al.

    The in vitro metabolism of ethynylestradiol, mestranol and levonorgestrel by human jejunal mucosa

    Br J Clin Pharmacol

    (1981)
  • DI Cargill et al.

    Fate of ingested radio labelled ethynylestradiol and its 3-cyclopentyl ether in patients with bile fistulas

    J Clin Endocrinol Metab

    (1969)
  • Cited by (31)

    • Gut microbiota and host Cyp450s co-contribute to pharmacokinetic variability in mice with non-alcoholic steatohepatitis: Effects vary from drug to drug

      2022, Journal of Advanced Research
      Citation Excerpt :

      Genetic abnormalities, disease states, orally administered adsorbents, and certain co-administered drugs all affect enterohepatic circulation. The gut microbiota is also a newly discovered factor affecting enterohepatic circulation [61,62]. The six probe drugs used in the present study are not excreted mainly through the gut and there is a relative dearth of information about the influence of enterohepatic circulation on these drugs, so we speculated that enterohepatic circulation might not contribute much to these drugs’ pharmacokinetic variabilities in NASH mice.

    • Oral contraceptive efficacy and antibiotic interaction: A myth debunked

      2002, Journal of the American Academy of Dermatology
    View all citing articles on Scopus
    View full text