Studies With 4-14c-Lynestrenol in Normal and Lactating Women

Abstract

4-14C-Lynestrenol** was administered either orally or by intravenous injection to women using Lyndiol®*** (5 mg lynestrenol + 150 μg mestranol). In order to study the effect of the pharmaceutical form in oral administration, the radioactive progestagen was given either as the pure compound in the form of a gelatin capsule or as a tablet containing all the ingredients usually present in Lyndiol®-tablets. The concentration of radioactivity in the blood and the excretion of radioactivity in the urine and milk of lactating women were then studied. The clearance rate of radioactivity from the blood was very low. A half-life in the order of 40 h was estimated for labelled »lynestrenol and metabolites«. Within 4–5 days after oral administration of a 14C-lynestrenol containing tablet, 54–65 % of the radioactivity was excreted in the urine, whereas much smaller amounts (in the order of 15 % of the administered dose) were excreted following oral administration of 14C-lynestrenol taken in a capsule. After intravenous administration 45–56 % of the administered radioactivity was recovered in the urine excreted within 4 days after injection. After oral administration of a 14C-lynestrenol containing tablet to 3 lactating women 0.022. 0.028 and 0.088 per cent of the administered radioactivity was excreted in the milk collected during the first 5 days after administration. The results indicate that resorption may be considerably influenced by the pharmaceutical form of the orally administered compound. For oral administration of 5 mg lynestrenol daily, as a Lyndiol®-tablet, it was calculated that in the order of 1 μg (0.02 % of the administered dose) of lynestrenol or its metabolites might be excreted per 100 ml of milk. These data are discussed with regard to the amount of steroids that might be transferred to infants during breast feeding when the mothers take oral contraceptives.

Metabolism of a new synthetic progestagen, Org 2969, in female volunteers. The distribution and excretion of radioactivity after an oral dose of the labelled drug

“…The figures for the urinary and faecal excretion of radioactivity after an oral Org 2969 dose are in the same range as reported for the other orally active progestagens (Layne et al 1963;Cooper & Kellie 1968;van der Molen et al 1969;Dorfman 1971;Gerhards et al 1971;Kishimoto et al 1972a,b).…”

Clinical Pharmacokinetics of Oral Contraceptive Steroids

“…Odlind et al (1979a) reported peak plasma norethisterone concentrations at 2 hours after oral doses of 0.5mg and 5mg oflynoestrenol, and Siekmann et al (1980) found peak plasma concentrations of norethisterone of 15 ng/ml after an oral dose of 2.Smg lynoestrenol. Van der Molen et al (1969) also examined the passage of radioactivity into the breast milk of women receiving a dose of 14C-Iynoestrenol. During long term therapy with lynoestrenol, plasma concentrations of norethisterone rise to greater levels than expected due to an effect on the SHBG capacity, but this was only seen if the dose was greater than 600#g daily (Odlind et aI., 1980).…”

Appearance of contraceptive steroids in human milk: effects on the child

“…With respect to the transfer studies using radioactive isotopes, these appear to have been done in the immediate post-partum week before lactation could be fully established, and since suckling had to be avoided, milk volumes where quoted tended to be low. Although the Laumas et al (1967) study, in which milk volumes obtained were not mentioned, indicated that up to 1-5% of the administered radioactive dose may be secreted in the milk, other studies by Van der Molen et al (1969) and Wijmenga et al (1969) in which milk volumes obtained were quoted have reported lower percentage recovery rates. It would be perhaps more important to undertake such studies after lactation has been fully established in mothers about to wean their infants, say around two months post-partum.…”