European Journal of Clinical Pharmacology

, Volume 15, Issue 5, pp 349–355 | Cite as

Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. Pharmacokinetics after an oral dose

  • L. Viinikka
  • O. Ylikorkala
  • R. Vihko
  • H. P. Wijnand
  • M. Booij
  • F. van der Veen
Originals

Summary

The pharmacokinetics of a new synthetic progestagen, Org 2969 (13-ethyl-11-methylene-18,19-dinor-17α-pregn-4-en-20-yn-17-ol) and its presumed active metabolite, 3-keto-Org 2969, were studied in five healthy female volunteers. During the first part of the study (Phase I), four volunteers ingested as a single dose 50 µg (about 100 µCi) of [16-3H]-Org 2969 together with 50 µg of ethinyl oestradiol. During the second part (Phase II), ten days of pretreatment with non-readioactive Org 2969 and ethinyl oestradiol preceded dosing, which was similar to that in Phase I. The fifth volunteer ingested 2500 µg of Org 2969 as a single dose. The concentrations of Org 2969 and 3-keto-Org 2969 in serum were measured by specific radioimmunoassay, and by as radioactivity. The maximum serum level of Org 2969 of 0.2–0.3% of the dose/litre was obtained 0.8–1.3 h after administration, and it was followed by a mono-exponential decrease, the half-life being 1.3–1.5 hours. No difference in Org 2969 levels was seen between Phase I and Phase II studies. The maximum 3-keto-Org 2969 serum level in Phase I was 0.4–0.8% of the dose/litre, 1–3 h after administration. A two-compartment open body model adequately described the data. The half-life of elimination was 16 hours. There was a considerable change in the single dose kinetics between Phase I and Phase II in the case of 3-keto-Org 2969. In Phase II the maximum serum level was 2.0–3.4% of the dose/litre, and there was no significant change in half-life. The change was considered to be due to a decrease in the apparent volume of distribution as a result of an increased number of binding sites on sex hormone-binding globulin induced by ethinyl oestradiol during the pretreatment period, and/or to an increase in the fraction of Org 2969 metabolized to 3-keto-Org 2969. The two simultaneous processes contributed to the change in kinetics and to the production of a steady state level of 3-keto-Org 2969 which resulted in a steady state within the first 10 days of daily administration of Org 2969 and ethinyl oestradiol.

Key words

contraception progestational steroid radioimmunoassay 

The following codes and trivial names were used

Org 2969

13-ethyl-11-methylene-18, 19-dinor-17α-pregn-4-en-20-yn-17-ol

3-keto-Org 2969

13-ethyl-17-hydroxy-11-methylene-18, 19-dinor-17α-pregn-4-en-20-yn-3-one

ethinyl oestradiol

17α-ethinyl-1,3,5(10)-oestratriene-3,17β-diol

lynestrenol

19-nor-17α-pregn-4-en-20-yn-17-ol

norgestrel

13-ethyl-17-hydroxy-18,19-dinor-17α-pregn-4-en-20-yn-3-one

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References

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Copyright information

© Springer-Verlag 1979

Authors and Affiliations

  • L. Viinikka
    • 1
  • O. Ylikorkala
    • 2
  • R. Vihko
    • 1
  • H. P. Wijnand
    • 3
  • M. Booij
    • 4
  • F. van der Veen
    • 3
  1. 1.Department of Clinical ChemistryUniversity of OuluFinland
  2. 2.Department of Obstetrics and GynaecologyUniversity of OuluFinland
  3. 3.Organon Scientific Development GroupOrganon Int., OssThe Netherlands
  4. 4.AKZO-Research LaboratoriesAnalogue Computer SectionArnhemThe Netherlands

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