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Kinetics of norethindrone in women; I. Radioimmunoassay and concentrations during multiple dosing
Author(s) -
Back D. J.,
Breckenridge A. M.,
Crawford Francesca E.,
McIver M.,
Orme M. L'E.,
Park B. K.,
Rowe P. H.,
Smith Eileen
Publication year - 1978
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1978244439
Subject(s) - radioimmunoassay , ethinylestradiol , endocrinology , medicine , pharmacokinetics , norethisterone , chemistry , dosing , sex hormone binding globulin , hormone , population , research methodology , androgen , environmental health
A radioimmunoassay for norethindrone has been developed with the use of an antiserum raised in rabbits after the injection of norethindrone‐3‐carboxymethyloxime linked to bovine serum albumin. The immunoassay is sensitive to 30 pg/ml norethindrone. With this assay plasma concentrations of norethindrone in 40 women receiving 1 mg norethindrone acetate with 50 µg ethinylestradiol were between 1.6 and 15.2 ng/ml 12 hr after dosing during multiple dosing. After a single dose of 1 mg of norethindrone acetate with 50 mg ethinylestradiol, the plasma half life (t½) of the terminal apparently monoexponential phase of norethindrone decay was between 6.1 and 12.3 hr in 6 patients. During long‐term therapy with contraceptive steroids the plasma t½ of norethindrone did not differ from the t½ after a single dose. In 4 women receiving contraceptive steroids for the first time. plasma concentrations of norethindrone rose progressively during the first cycle to concentrations higher than predicted from simple accumulation pharmacokinetics. The sex hormone‐binding globulin capacity also increased and there was a good correlation between the plasma concentration of norethindrone and the sex hormone‐binding capacity (r between 0.695 and 0.910 in 4 patients). In 3 women starting the contraceptive steroid 4 wk postpartum there was a reduction of plasma norethindrone concentration with time (r = 0.528 p < 0.01) and this correlated with a fall in the sex hormone‐binding capacity (p < 0.05). In women taking a preparation containing 3 mg norethindrone acetate. the mean plasma norethindrone concentration was only 1.4 times as high as that in women taking 1 mg norethindrone acetate.