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Pulsed estrogen therapy: pharmacokinetics of intranasal 17-beta-estradiol (S21400) in postmenopausal women and comparison with oral and transdermal formulations

European Journal of Drug Metabolism and Pharmacokinetics volume 24, pages 265–271 (1999)Cite this article

Summary

Pharmacokinetics of estradiol and estrone were assessed in postmenopausal women receiving S21400, a novel 17β-estradiol formulation administered by nasal route; the results were compared with those obtained with oral and transdermal routes. Thirty six women received three treatments: a specified dose of 17β-estradiol (100, 300 or 450 μg) given once and as 2 doses, 12 h apart, using three parallel dose groups in a randomised, crossover study. Thereafter, a reservoir patch (50 μg/day of 17β-estradiol) or a tablet of 2 mg micronised 17β-estradiol were randomly administered. Plasma concentrations of estradiol and estrone were measured by radioimmunoassays. Following intranasal dosing, estradiol was rapidly absorbed with plasma concentrations reaching maximal values (approximately 1400 pg/ml with a single 300 μg dose) after 10–30 min and returning within 12 h to levels of untreated postmenopausal women. Systemic exposure to estradiol was dose proportional and independent of the treatment regimen. Moreover, the dose of 300 μg gave an estimated 24 h systemic exposure to exogenous estradiol close to that of the 50 μg/day reservoir patch or the 2 mg tablet. The mean estrone to estradiol ratio was similar and 4-fold lower than those with the patch and the tablet, respectively. In conclusion, by this new route for estrogen replacement therapy, the nasal route, the pharmacokinetics of estradiol as S21400 were linear and displayed a ‘pulsed’ kinetic profile, different from those obtained with the usual routes of administration.

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References

  1. Hargrove J.T., Eisenberg E. (1995): Menopause. Med. Clin. North Am., 79: 1337–1356.

    PubMed  CAS  Google Scholar 

  2. Lievertz R.W. (1987): Pharmacology and pharmacokinetics of estrogens. Am. J. Obstet. Gynecol., 156: 1289–1293.

    PubMed  CAS  Google Scholar 

  3. Judd H.L. (1987): Oestrogen replacement therapy: physiological considerations and new applications. Baillièrse’s Clin. Endocrinol. Metab., 1, 177–206.

    CAS  Google Scholar 

  4. Kuhnz W., Gansau C., Mahler M. (1993): Pharmacokinetics of estradiol, free and total estrone, in young women following single intravenous and oral administration of 17β-estradiol. Arzneimittelforschung, 43: 966–973.

    PubMed  CAS  Google Scholar 

  5. Steingold K.A., Laufer L., Chetkowski R.J. et al. (1985): Treatment of hot flushes with transdermal estradiol treatment. J. Clin. Endocrinol. Metab., 61: 627–632.

    Article  PubMed  CAS  Google Scholar 

  6. Selby P.L., McGarricle H.H.G., Peacock M. (1989): Comparison of the effects of oral and transdermal oestradiol administration on oestrogen metabolism, protein synthesis, gonadotrophin release, bone turnover and climacteric symptoms in postmenopausal women. Clin. Endocrinol., 30: 241–249.

    Article  CAS  Google Scholar 

  7. McBurney E.I., Noel S.B., Collins J.H. (1989): Contact dermatitis to transdermal estradiol system. J. Am. Acad. Dermatol., 20: 508–510.

    Article  PubMed  CAS  Google Scholar 

  8. Hermens W.A., Belder C.W., Merkus J.M., Hooymans P.M., Verhoef J., Merkus F.W. (1991): Intranasal estradiol administration to oophorectomized women. Eur. J. Obstet. Gynecol. Reprod. Biol., 40: 35–41.

    Article  PubMed  CAS  Google Scholar 

  9. Peron P.G., Cladwell B.V. (Eds) (1970): Immunological methods in steroid determination. New York: Century-Crafts, 87–112.

    Google Scholar 

  10. Toutain P.L. (1995): QL-KINTOOL version 3.1. Pharmacokinetic software. Qualilab, 72, Quai du Châtelet, 45000 Orleans, France.

  11. Yamaoka K., Nakagawa T., Uno T. (1978): Application of Akaike’s Information Criterion (AIC) in the evaluation of linear pharmacokinetic equations. J. Pharmacokinet. Biopharm., 6: 165–175.

    Article  PubMed  CAS  Google Scholar 

  12. Berner B., John V.A. (1994): Pharmacokinetic characterisation of transdermal delivery systems. Clin. Pharmacokinet., 26: 121–134.

    Article  PubMed  CAS  Google Scholar 

  13. Marty J.P. (1996): New trends in transdermal technologies: development of the skin patch, Menorest®. Int. J. Gynecol. Obstet., 52: S17-S20.

    CAS  Google Scholar 

  14. Hankinson S.E., Willett W.C., Manson J.E. et al. (1995): Alcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women. J. Natl Cancer Inst., 87: 1297–1302.

    Article  PubMed  CAS  Google Scholar 

  15. Müller P., Botta L., Ezzet F. (1996): Bioavailability of estradiol from a new matrix and a conventional reservoir-type transdermal therapeutic system. Eur. J. Clin. Pharmacol., 51:327–330.

    Article  PubMed  Google Scholar 

  16. Scott R.T., Ross B., Anderson C., Archer D.F. (1991): Pharmacokinetics of percutaneous estradiol: a crossover study using a gel and a transdermal system in comparison with oral micronized estradiol. Obstet. Gynecol., 77: 758–764.

    PubMed  Google Scholar 

  17. Marty J-P. (1996): Menorest: technical development and pharmacokinetic profile. Eur. J. Obstet. Gynecol., 64: S29-S33.

    Article  CAS  Google Scholar 

  18. Fink B.J., Christensen M.S. (1981): Bioavailability of oestradiol and oestriol administered orally to oophorectomized women. Maturitas, 3: 289–294.

    Article  PubMed  CAS  Google Scholar 

  19. Studd J., Pornel B., Marton I. et al. (1999): Dose-response study of the efficacy and acceptability of intra-nasal 17-β estradiol. Lancet, 353: 1574–1578.

    Article  PubMed  CAS  Google Scholar 

  20. Kronenberg F. (1990): Hot flushes: epidemiology and physiology. Ann. N. Y. Acad. Sci., 592: 52–86.

    Article  PubMed  CAS  Google Scholar 

  21. Kuttenn F. (1993): Traitement de la ménopause. Rev. Prat. (Paris), 43: 2593–2595.

    CAS  Google Scholar 

  22. Lindsay R., Dempster D.W., Jordan V.C. (Eds) (1997): Estrogens and antiestrogens: basic and clinical aspects. Philadelphia: Lapincott-Raven, 43–62.

    Google Scholar 

  23. Lobo R.A., Cassidenti D.L. (1992): Pharmacokinetics of oral 17β-estradiol. J. Reprod. Med., 37: 77–83.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Unit of clinical Pharmacology, Versus, Aubervilliers, France

    N. Brion

  2. Technologie Servier, Orléans, France

    O. Lhote

  3. Institut de Recherches Internationales Servier, Courbevoie, France

    P. Deloffre

  4. UMR CNRS 8612, Faculty of Pharmacy, University of Paris Sud, 5 rue Jean-Baptiste Clement, F-92296, Chatenay Malabry Cedex, France

    J-Ph. Devissaguet

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  1. J-Ph. Devissaguet
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Devissaguet, JP., Brion, N., Lhote, O. et al. Pulsed estrogen therapy: pharmacokinetics of intranasal 17-beta-estradiol (S21400) in postmenopausal women and comparison with oral and transdermal formulations. Eur. J. Drug Metab. Pharmacokinet. 24, 265–271 (1999). https://doi.org/10.1007/BF03190030

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  • DOI: https://doi.org/10.1007/BF03190030

Keywords

  • Estradiol
  • estrone
  • pharmacokientics
  • intranasal
  • postmenopausal