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The myometrium of the rabbit contains a 17-β-hydroxysteroid : NAD(P) oxidoreductase, whose specific activity depends on the functional state of the uterus. In pregnancy one observes a 25-fold increase and after parenteral administration of oestradiol or stilboestrol an approximately 50-fold increase compared to the normal adult rabbit. The enzyme was purified from myometrium about 100-fold by precipitation twice with ammonium sulfate and by gel filtration. The enzyme was assayed by incubation with [16-14C]oestradiol-17β, determining oestron as the reaction product. Specific activity was expressed as n-moles oestron/60 min/mg protein. The molecular weight of the 17-β-hydroxysteroid : NAD(P) oxidoreductase can be estimated from gel filtration studies in the range from 10,000 to 50,000. The enzyme requires NAD+ or NADP+ as cofactor, NADP+ giving a 20% lower activity than an equimolar amount of NAD+. The optimal pH for the enzymatic oxidation of oestradiol to oestron is 9.4, and for the reduction of oestron to oestradiol 6.4. The Michaelis-Menten constant for oestradiol is 7.6 × 10-6 M. The oxidation of testosterone is at least 100 times slower than that of oestradiol. In phosphate-free buffer solutions, the addition of phosphate gives an increase of the enzyme activity. p-Chlormercuribenzoic acid (10-4 M) and o-iodosobenzoic acid (10-4 M) inhibit the activity of 17-β-hydroxysteroid: NAD(P)oxidoreductase of the myometrium by 97% and 26%, respectively. [ABSTRACT FROM AUTHOR]

The serum concentrations of gestodene (CAS 60282-87-3) as well as the binding of this progestin to serum proteins were studied in 40 women who took a low-dose oral contraceptive (Femovan, Femodene) containing 30 micrograms ethinyl estradiol (CAS 57-63-6) and 75 micrograms gestodene for 3 months. On days 1, 10, and 21 of the first and the third treatment cycle, respectively, 7 blood samples were drawn before and up to 4 h after pill intake; additional samples were taken prior to morning ingestion of pill on days 2, 5, 11, 15 and 22 of these cycles. Gestodene levels were measured by means of a specific radioimmunoassay and were evaluated for Cmax, tmax, and AUC up to 4 and 24 h. Independent of the test day and the treatment cycle studied, mean maximum gestodene serum levels were found about 0.8 to 0.9 h after pill intake. During the first treatment cycle, mean values of Cmax, AUC(0-4h), and AUC(0-24h) amounted to 4.3 ng.ml-1, 9.3 ng.ml-1.h, and 27.3 ng.ml-1.h on test day 1; these values increased by 250-400% and by 300-500%, respectively, when days 10 and 21 were compared to day 1. On day 1 of the third treatment cycle, these pharmacokinetic parameters were higher by almost a factor of two as compared to the corresponding data obtained on the beginning of the first cycle whereas the increase of these values between day 1 and the subsequent test days (200-300%) was slightly lower in cycle 3 as compared to cycle 1.(ABSTRACT TRUNCATED AT 250 WORDS)

The serum concentrations of 3-keto-desogestrel have been measured in 43 women who took a low-dose oral contraceptive containing 30 micrograms ethinyl estradiol (CAS 57-63-6) together with 150 micrograms desogestrel (CAS 54024-22-5) for a period of 3 months. Basic pharmacokinetic parameters, like Cmax, tmax and AUC, as well as the serum protein binding of 3-keto-desogestrel were determined on days 1, 10 and 21 of the first and the third treatment cycle, respectively. During cycle one, Cmax, AUC(0-4h) and AUC(0-24h) values on day 1 were 1.9 +/- 0.7 ng/ml, 3.9 +/- 1.3 ng.ml-1.h and 12.4 +/- 5.7 ng.ml-1.h, respectively. These values increased to 4.7 +/- 2.0 ng/ml, 12.1 +/- 5.6 ng.ml-1.h and 47.3 +/- 26.0 ng.ml-1.h on day 21. Within cycle 3, a similar, although less steep increase was observed for these parameters and there was practically no difference in the values of corresponding parameters on day 21 of both cycles. Throughout treatment, there was a redistribution of 3-keto-desogestrel with respect to the binding proteins albumin and sex hormone binding globulin (SHBG). During cycle 1, the free fraction decreased from 1.8% on day 1 to 1.1% on day 21, and the SHBG-bound fraction increased at the same time from 40% to 62%, mainly at the expense of the albumin-bound fraction. During cycle 3, there were only minor changes as compared to cycle one. The observed changes in the serum protein binding were related to an increase in SHBG levels during the treatment period.