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Effect of rifampicin.treatment on the metabolism of oestradiol and 17α-ethinyloestradiol by human liver microsomes

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Summary

Liver biopsies were obtained from four patients treated with rifampicin 600 mg for 6–10 days. Hepatic microsomes were incubated with an NADPH-regenerating system and the substrates [2, 4, 6, 7--3H] oestradiol, [6, 7-3H] oestradiol, [2, 4, 6, 7-3H] ethinyloestradiol and [6, 7-3H] ethinyloestradiol. The hydroxylation rates of these steroids at the labelled positions of rings A and B were determined by measuring the transformation of tritium into HTO by the microsomal enzymes. Comparison with previously published data showed that treatment with rifampicin caused a fourfold increase in the rate of hydroxylation of oestradiol and ethinyloestradiol at positions C-2/C-4 of ring A and C-6/C-7 of ring B. The acceleration of oestrogen hydroxylation by rifampicin was paralleled by an increase in microsomal cytochrome P-450, and also by microsomal reduction of rifampicin-quinone, a reactive metabolite of rifampicin. The increased aromatic hydroxylation of oestradiol and ethinyloestradiol leads to enhancement of their irreversible binding to microsomal protein. The data provide an explanation for the diminished efficacy of oestrogens in contraceptive formulations given to patients under treatment with rifampicin.

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Authors and Affiliations

  1. Institut für Toxikologie der Universität Tübingen, Wilhelmstr. 56, D-74, Tübingen 1, Federal Republic of Germany

    H. M. Bolt, H. Kappus & M. Bolt

  2. Innere Abteilung, Kreiskrankenhaus Böblingen, Böblingen, Federal Republic of Germany

    H. M. Bolt, H. Kappus & M. Bolt

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  1. H. M. Bolt
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  2. H. Kappus
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  3. M. Bolt
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Part of the results described in this paper has been presented in preliminary form (Bolt, Kappus and Bolt, 1974a)

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Bolt, H.M., Kappus, H. & Bolt, M. Effect of rifampicin.treatment on the metabolism of oestradiol and 17α-ethinyloestradiol by human liver microsomes. Eur J Clin Pharmacol 8, 301–307 (1975). https://doi.org/10.1007/BF00562654

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  • DOI: https://doi.org/10.1007/BF00562654

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