The plasma concentrations of 3-keto-desogestrel have been measured by radioimmunoassay in a crossover study in nine healthy female volunteers given oral desogestrel (150 micrograms) and ethinyloestradiol (30 micrograms) and intravenous (i.v.) 3-keto-desogestrel (150 micrograms) and ethinyloestradiol (30 micrograms). Bioavailability ranged between 40.0 and 113% with a mean value ( +/- SD) of 76.1 +/- 22.5%. Only 3 subjects had a bioavailability of less than 70%. There was no significant difference in the elimination half life of 3-keto-desogestrel which was 12.6 +/- 4.1h following i.v. administration and 11.9 +/- 4.1h after oral administration of desogestrel.
PIP: In order to define its bioavailability, plasma concentration of 3-keto-desogestrel, the active metabolite of the progestogen desogestrel, was radioimmunoassayed in 9 women after a single iv dose of 150 ug or a single oral dose of 150 ug in combination with 30 ug ethinyl estradiol. Desogestrel is 13-ethyl-11-methylene-18, 19-dinor-17alpha-preg-4-en-20-yn-17-ol, the progestogen in the effective combined oral contraceptive Marvelon (Organon). The drug was given early in the menstrual cycle to each woman twice in a crossover design, 4 weeks apart. Bioavailability was calculated as the ratio of area under the plasma concentration time curve of the oral to the area under the curve of the iv dose. There was no significant difference in the elimination half-life of 3-keto-desogestrel by oral or iv administration: 11.9 and 12.6 hours. Mean plasma clearance, calculated by dose given divided by area under the curve, was 12.13 1/hour by oral, and 8.7 by iv routes. Bioavailability ranged from 40 to 113%, a wide individual variation, as seen in previous studies. Although mean bioavailability was 76%, the value was above 70% in 6 women, and 40.0, 54.7 and 64.1% in 3 others. This indicates that bioconversion was near quantitative. The reason for the variation cannot be ascertained from these data. Despite variability in bioavailability, the desogestrel combined oral contraceptive is reported to be very effective, as well as less androgenic than pills containing levonorgestrel.