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Pharmacokinetic evaluation of oral 17β-oestradiol and two different fat soluble analogues in ovariectomized women

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Summary

A randomised, single-blind comparative study was carried out in 9 ovariectomized women to evaluate the kinetics of single doses of three different steroid combinations: 0.150 mg desogestrel +2.0 mg micronized 17β-oestradiol, 0.150 mg desogestrel +0.500 mg 17β-oestradiol cyclo-octyl acetate and 0.150 mg desogestrel +1.0 mg 17β-oestradiol decanoate. Serum levels of 17β-oestradiol and oestrone were measured, as well as the excretion of 17β-oestradiol and its metabolites (oestrone and oestriol) in urine.

In relation to the doses given, higher peak serum concentrations of 17β-oestradiol were obtained after the two fat soluble analogues, while the AUCs were similar to that after micronised 17β-oestradiol. However, there was more extensive conversion of the micronised 17β-oestradiol preparation into oestrone compared to 17β-oestradiol cyclo-octyl acetate and 17β-oestradiol decanoate. The oestrone/17β-oestradiol serum concentration ratio was approximately 2.6 before tablet intake and remained essentially unchanged after intake of 17β-oestradiol cyclo-octyl acetate and 17β-oestradiol decanoate. After micronized 17β-oestradiol however, there was a 2–3-fold increase in the ratio at Cmax and slower elimination of 17β-oestradiol from plasma, which may be due to the fact that high serum oestrone levels may serve as a reservoir, since both a metabolite and also a precursor of 17β-oestradiol.

The urinary excretion of 17β-oestradiol, oestrone and oestriol was highest after oral administration of micronized 17β-oestradiol compared to 17β-oestradiol cyclo-octyl acetate and 17β-oestradiol decanoate. The time pattern of urinary excretion reflected the serum concentration profiles of the preparations given.

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Authors and Affiliations

  1. Department of Obstetrics and Gynaecology, University of Göteborg, East Hospital, Göteborg, Sweden

    W. Schubert & G. Cullberg

  2. Division of Clinical Pharmacology, University of Göteborg, Sahlgrenska Hospital, Göteborg, Sweden

    T. Hedner

  3. Gynekologgruppen, Kungsgatan 32, S-411 19, Göteborg, Sweden

    W. Schubert

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  1. W. Schubert
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  2. G. Cullberg
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  3. T. Hedner
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Schubert, W., Cullberg, G. & Hedner, T. Pharmacokinetic evaluation of oral 17β-oestradiol and two different fat soluble analogues in ovariectomized women. Eur J Clin Pharmacol 44, 563–568 (1993). https://doi.org/10.1007/BF02440860

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  • DOI: https://doi.org/10.1007/BF02440860

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