ABSTRACT
Levels of norethisterone and medroxyprogesterone acetate were measured in serum and milk of women receiving the injectable contraceptive formulations Norigest and DepoProvera, respectively, throughout complete injection intervals. In 5 of 10 women receiving Norigest, serum norethisterone levels were undetectable by 8 weeks after injection and only 2 women had detectable levels of norethisterone in milk at this time. In contrast, 8 of 10 women receiving DepoProvera had detectable levels of medroxyprogesterone acetate in both serum and milk 12 weeks after injection. The ratio of the milk:serum concentrations of norethisterone varied from 0.12 to 0.92 (mean 0.34) and for medroxyprogesterone acetate from 0.12 to 2.60 (mean 0.88). It is unlikely that these differences between the two formulations are due entirely to differences between the binding of norethisterone and medroxyprogesterone acetate to serum proteins. The area under the curve of serum steroid concentrations plotted against time was only 50% higher for women injected with DepoPovera than for those injected with Norigest but the area under the curve for milk values was 400 times higher. Assuming the infant ingests 600 ml daily, the daily intake of steroids in the first week after injection would be 0.5 to 2.4 micrograms for norethisterone and 1 to 13 micrograms for medroxyprogesterone acetate. By 8 weeks after injection, the amount of norethisterone ingested would be small but that of medroxyprogesterone acetate would still be significant.
Subject(s)
Contraceptive Agents, Female/metabolism , Medroxyprogesterone/analogs & derivatives , Milk, Human/metabolism , Norethindrone/metabolism , Adult , Body Weight/drug effects , Contraceptives, Oral , Female , Humans , Injections, Intramuscular , Medroxyprogesterone/administration & dosage , Medroxyprogesterone/metabolism , Medroxyprogesterone Acetate , Norethindrone/administration & dosageABSTRACT
The pharmacokinetics of a dose of 50 microgram ethynyloestradiol administered orally was studied in fourteen centres. Absorption was rapid and the highest serum concentrations of total ethynyloestradiol were found in most subjects at 1 h and by 24 h concentrations were less than 250 pg/ml. Calculation of the half-lives for absorption, distribution and elimination showed wide variations between subjects, the half-life of elimination varying from 2.5 h to more than 30 h. Bioavailability as measured by the area under the serum ethynyloestradiol concentration-time curve also showed more than a ten-fold variation. Intra-centre differences in the various parameters measured were as large as the inter-centre differences.
Subject(s)
Ethinyl Estradiol/metabolism , Biological Availability , Ethinyl Estradiol/administration & dosage , Ethinyl Estradiol/blood , Female , Half-Life , Humans , Kinetics , Norethindrone/administration & dosageABSTRACT
The rate of metabolism of orally administered norethisterone was compared in fourteen centres by measuring plasma levels of the steroid by radioimmunoassay at varying times after oral administration of a 1 mg dose. The inter-centre differences were of the same order as the intra-centre differences. Variations in metabolism appeared not to be due to variations in body size.
