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Pharmacokinetics and bioavailability of ST 1435 administered by different routes

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      Abstract

      The ovulation inhibiting potency of the synthetic progestin ST 1435 (Nestorone™) is high after parenteral administration and practically nil after oral administration. The purpose of this study was to determine the pharmacokinetic parameters of ST 1435 after single oral or intravenous administration or after long-term treatment with sub-dermal implants in women. After administration, as a single i.v. bolus, the plasma disappearance rate of immunoreactive ST 1435 had two components with half-lives (mean ± SE) of 3.5 ± 0.5 and 83 ± 14 min, respectively. The volume of distribution was 4.7 ± 1.3 L/Kg and the metabolic clearance rate was 55 ± 6 L/Kg/d. After oral administration, the bioavailability was about 10% of the dose. After chronic subdermal administration, the plasmatic clearance was slower than following the acute doses. These results show that ST 1435 has shorter half-lives and a faster clearance rate than progestins which bind SHBG. The large volume of distribution indicates accumulation in the extra-vascular space and was expected in view of the high affinity of ST 1435 for progesterone receptors. The slower plasma elimination rate after chronic administration was attributed to the re-entry of a larger mass of drug from the extravascular space, and/or accumulation of immunoreactive metabolites with slower clearance than the parent steroid.
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      References

        • Croxatto HB
        • Díaz S
        • Peralta O
        • et al.
        Fertility regulation in nursing women. IV. Long-term influence of a low-dose combined oral contraceptive initiated at day 30 postpartum upon lactation and infant growth.
        Contraception. 1983; 27: 13-25
        • Peralta O
        • Díaz S
        • Juez G
        • et al.
        Fertility regulation in nursing women. V. Long-term influence of a low-dose combined oral contraceptive initiated at day 90 postpartum upon lactation and infant growth.
        Contraception. 1983; 27: 27-38
        • Coutihno EM
        • Da Silva AR
        • Kraft H-G
        Fertility control with subdermal Silastic capsules containing a new progestin (ST 4135).
        Int J Fertil. 1976; 21: 103-108
        • Laurikka-Routti M
        • Haukkamaa M
        • Lähteenmäki P
        Suppression of ovarian function with the transdermally given synthetic progestin ST 1435.
        Fertil Steril. 1992; 58: 680-689
        • Croxatto HB
        • Díaz S
        The place of progesterone in human contraception.
        J Steroid Biochem. 1987; 27: 991-994
        • Lähteenmäki P.L.A.
        • Díaz S
        • Miranda P
        • Croxatto HB
        • Lähteenmäki P
        Milk and plasma concentrations of the progestin ST 1435 in women treated paren-terally with ST 1435.
        Contraception. 1990; 42: 555-562
        • Lähteenmäki P
        • Weiner E
        • Lähteenmäki P
        • Johansson E.D.B.
        • Luukkainen T
        Contraception with subcutaneous capsules containing ST 1435. Pituitary and ovarian function and plasma levels of ST 1435.
        Contraception. 1981; 23: 63-75
        • Fotherby K
        Potency and pharmacokinetics of gestagens.
        Contraception. 1990; 41: 533-550
        • Lähteenmäki P
        • Hammond G
        • Luukkainen T
        Serum non-protein bound percentage and distribution of the progestin ST 1435: no effect of ST 1435 treatment on plasma SHBG and CBG binding capacities.
        Acta Endocrinologica. 1983; 102: 307-313
        • Odlind V
        • Lithell H
        • Kurunmäki H
        • et al.
        ST 1435: Development of an implant.
        in: Zatuchni GI Goldsmith A Shelton JD Sciarra JJ Long-acting Contraceptive Delivery Systems. Harper and Row, Philadelphia1984: 441-449
        • Lähteenmäki P.L.A.
        Intestinal absorption of ST 1435 in rats.
        Contraception. 1984; 30: 143-151