Pharmacokinetics and serum protein binding of 3-keto-desogestrel in women during three cycles of treatment with a low-dose combination oral contraceptive.
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.
Kuhnz
W
W
Research Laboratory, Schering Aktiengesellschaft, Berlin/Bergkamen, Fed. Rep. of Germany.
al-Yacoub
G
G
Power
J
J
Ormesher
S E
SE
Back
D J
DJ
Jütting
G
G
D000328:Adult; D001798:Blood Proteins / Q000378:metabolism; D001835:Body Weight; D003429:Cross Reactions; D017135:Desogestrel / Q000097:blood / Q000276:immunology / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D011485:Protein Binding
D001798:Blood Proteins; C044815:etonogestrel; D017135:Desogestrel