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Pharmacokinetics of progesterone in postmenopausal women:

1. Pharmacokinetics following intravaginal administration
  • C. Mircioiu
  • A. Perju
  • A. Neagu
  • E. Griu
  • G. Calin
  • D. S. Miron
Article

Summary

Progesterone was administered to postmenopausal women in a form of vaginal suppositories containing 100 and 200 mg active substance inButyrum cacao (BC) andMassa estarinum (ME), a base with emulsifying properties. In the case of single doses, blood samples were taken at 2, 4, 6, 24, 48 and 72 h. Another group of patients received vaginal suppositories (100 mg progesterone) once a day for a 6 day period, with blood samples taken 12 h after each administration. The plasma levels of progesterone were evaluated by radioimmunoassay. The time of maximum concentration (tmax) was 4 h in most cases, and 6 h in the others. The plasma levels were not dose-proportional. Peak plasma concentrations were in the range of 10–15 ng/ml with a mean of 10.5 ng/ml for the 100 mg and 12 ng/ml for the 200 mg doses. The ratio of the mean area under the curve (AUC) for 200 mg and the mean AUC for the 100 mg dose was found to be 1.37. Replacing BC with ME resulted in the lowering of cmax and AUC, and an increase in tmax following a reducing in the rate and extent of adsorption. In the case of ME suppositories, the variability in AUC, cmax and tmax was greater compared to that observed with the BC suppositories. Elimination half-time was in the range of 9–10 h for BC and 14 h for ME suppositories. In vitro assessment of the release kinetics from a hydrophobic and an emulsion type base confirmed previous findings: the latter base assured better pharmaceutical availability. The repeated doses did not seem to produce an accumulation of progesterone in the plasma. On the contrary, a small decrease in plasma levels over time appeared during the 6 day period. Numerical analysis revealed an excellent goodness of fit for the in vivo experimental data via biexponential curves, i.e. a pseudomonocompartmental model.

Keywords

Progesterone pharmacokinetics vaginal suppositories 

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References

  1. 1.
    Check J.H., Rankin A., Teichman M. (1986): The risk of fetal anomalies as a result of progesterone therapy during pregnancy. Fertil. Steril., 45, 575–577.PubMedGoogle Scholar
  2. 2.
    Lobo R.A., Whithead M.I. (Eds) 1989: Proceedings of the consensus development conference on progesterone. New York: Worldwide Medical Group.Google Scholar
  3. 3.
    Morville R., Dray F., Reynier J., Barrat J. (1982): Biodisponibilité de la progesterone naturelle administrée par voie orale. J. Gynecol. Obstet. Biol. Reprod., 11, 355–363.Google Scholar
  4. 4.
    Ottosson U.B., Carlstrom K., Damber J.E., Von Schoultz B. (1984): Serum levels of progesterone and some of its metabolites including deoxycorticosterone after oral and parenteral administration. Br. J. Obstet. Gynaecol., 91, 1111–1119.Google Scholar
  5. 5.
    Padwick M., Endacott J., Manson C., Whithead M. (1986): Adsorption and metabolism of oral progesterone when administered twice daily. Fertil. Steril., 46, 402–407.PubMedGoogle Scholar
  6. 6.
    Nillius S.J., Johansson E.D.B. (1971): Plasma levels of progesterone after vaginal, rectal or intramuscular administration of progesterone. Am. J. Obstet. Gynecol., 110, 470–477.PubMedGoogle Scholar
  7. 7.
    Fulper L.D., Cleary R.V., Harland E.C., Hilkan A.H., Jones A.B. (1987): Comparison of serum progesterone levels in dogs after administration of progesterone by vaginal tablet and vaginal suppositories. Am. J. Obstet. Gynecol., 156, 253–259.PubMedGoogle Scholar
  8. 8.
    Chakmakjian Z.H., Zachariah N.Y. (1987): Bioavailability of progesterone with different modes of administration. J. Reprod. Med., 32, 443–448.PubMedGoogle Scholar
  9. 9.
    Dalton K. (1988): Treatment of premenstrual syndrome. B.M.J., 297: 490.CrossRefGoogle Scholar
  10. 10.
    Hanson W.A. (1982): Handbook of Dissolution Testing. Springfield, IL: Pharmaceutical Technology.Google Scholar
  11. 11.
    Heinzel G., Woloszczak R., Thomann P. (1993): Pharmacokinetic and pharmacodynamic data analysis system. Stuttgart: Gustav Fischer.Google Scholar
  12. 12.
    Erny R., Simoncini C., Chastelliere N., de Ligneres B. (1989): Variations de la progesterone plasmatique induites par l’administration vaginale d’Utrogestan. J. Gynecol. Obstet. Biol. Reprod., 18, 229–234.Google Scholar
  13. 13.
    Simon J.A., Robinson D.E., Andrews M.C. et al. (1993): The absorption of oral micronized progesterone: the effect of food, dose proportionality, and comparison with intramuscular progesterone. Fertil. Steril. 60, 26–33.PubMedGoogle Scholar
  14. 14.
    Archer D.F., Fahy G.E., Viniegra-Sibal A. (1995): Initial and steady-state pharmacokinetics of a vaginally administered formulation of progesterone. Am. J. Obstet. Gynecol., 173, 471–478.CrossRefPubMedGoogle Scholar
  15. 15.
    Glazener M.A., Bailay I., Hull M.G.R. (1985): Effectiveness of vaginal administration of progesterone. Br. J. Obstet. Gynaecol., 92, 364–368.PubMedGoogle Scholar
  16. 16.
    Norman T.R., Morse A.C., Dennerstein L. (1991): Comparative bioavailability of orally and vaginally administered progesterone. Fertil. Steril., 56, 1034–1039.PubMedGoogle Scholar
  17. 17.
    Maddocks S., Hahn P., Moller F., Reid R.I. (1986): A double blind placebo-controlled trial of progesterone vaginal suppositories in the treatment of premenstrual syndrome. Am. J. Obstet. Gynecol., 154, 573–581.PubMedGoogle Scholar
  18. 18.
    Thihssen J.H., Zander J. (1966): Progesterone 4 C14 and its metabolites in the blood after intravenous injections into women. Acta Endocrinol., 51, 563.Google Scholar
  19. 19.
    Glazener M.A., Bailay I., Hull M.G.R. (1985): Effectiveness of vaginal administration of progesterone. Br. J. Obstet. Gynaecol., 92, 364–368.PubMedGoogle Scholar
  20. 20.
    Mircioiu C., Perju A., Enachescu D., Griu E., Neagu A. (1993): Biodisposition and pharmacokinetics of percutaneous and intravaginal progesterone. Correlation with in vitro measurements. 3rd Int. Conf. on Prediction Penetration, La Grande Motte, France, 14–16 April, 1993.Google Scholar
  21. 21.
    Mircioiu C. (1994): Pseudomonocompartmental behaviour of the pharmacokinetics of some topical applied lipophilic drugs. Clin. Trials Meta-Anal., 29, 295.Google Scholar

Copyright information

© Springer-Verlag 1998

Authors and Affiliations

  • C. Mircioiu
    • 1
  • A. Perju
    • 1
  • A. Neagu
    • 1
  • E. Griu
    • 1
  • G. Calin
    • 1
  • D. S. Miron
    • 1
  1. 1.Faculty of PharmacyCarol Davila University of Medicine and PharmacyBucharestRomania

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