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.
PIP: In Germany, health workers drew serum samples from 43 healthy young women who used a low dose oral contraceptive with 30 mcg ethinyl estradiol and 150 mcg desogestrel for 3 treatment cycles to measure 3-Keto-desogestrel (KDG) levels and determine serum protein binding proteins. The mean maximum KDG level on test day 1 was 1.9 ng/ml during the first treatment cycle. The area under the curve zero to 4 hours after pill intake was 3.9 ng ml-1 and, zero to 24 hours after intake, it was 12.4 ng ml-1. These figures rose to 4.7 ng/ml, 12.1 ng ml-1, and 47.3 ng ml-1, respectively on day 21. During the third treatment cycle, the increase was somewhat lower than it was during the first cycle. Further, the figures of the corresponding parameters on day 21 of both cycles, 1 and 3 barely changed. Between day 1 and 21, the free fraction of KDG fell from 1.8% to 1.1% while the sex hormone binding globulin (SHBG) bound fraction of KDG rose from 40% to 62%. This increase was largely at the expense of the albumin bound fraction (decrease from 32.2-26.1%). Just slight changes occurred during cycle 3. Women with lower body weights had significantly higher KDG serum levels than those with higher body weights (p .05). The results on serum protein binding of KDG can help researchers interpret overall pharmacokinetic changes.