Pharmacokinetics and serum protein binding of gestodene and 3-keto-desogestrel in women after single oral administration of two different contraceptive formulations

Arzneimittelforschung. 1992 Sep;42(9):1139-41.


Two low-dose oral contraceptives, both containing the same dose of ethinyl estradiol (EE2, CAS 57-63-6) but different progestins--gestodene (CAS 60282-87-3) and desogestrel (CAS 54024-22-5), respectively--were administered to 18 women in a single dose, cross-over study. The serum concentrations of gestodene (GEST, one of the components of Femovan) and 3-keto-desogestrel (KDG) have been measured by specific radioimmuno-assays and the pharmacokinetics of both progestins were assessed. The serum protein binding of both compounds was also investigated and although the free fraction was the same for GEST and KDG, the distribution with respect to the binding proteins albumin and sex hormone binding globulin (SHBG) was slightly different. GEST was mainly bound to SHBG, while KDG was predominantly bound to albumin. Maximum concentrations of GEST were observed after 0.7 +/- 0.2 h and amounted to 4.9 +/- 2.4 ng/ml. A biphasic pattern of disposition was observed, with half lives of 0.13 +/- 0.06 h and 14.6 +/- 4.2 h, respectively. The AUC was 32.9 +/- 18.3 For KDG, maximum serum levels of 1.7 +/- 0.8 ng/ml were observed 1.5 +/- 0.8 h post administration. Drug levels declined with half-lives of 0.5 +/- 0.2 h and 17.0 +/- 9.3 h, respectively, and the AUC was 15.2 +/- 10.9

PIP: In Berlin, Germany and Liverpool, England health workers took blood samples from 18 24-34 year old women who took either a single oral contraceptive pill (Femovan) with 75 mcg gestodene and 30 mcg ethinyl and 30 mcg ethinyl estradiol or a single oral contraceptive pill with 150 mcg desogestrel and 30 mcg ethinyl estradiol followed 7 days later by a single pill with 75 mcg gestodene and 30 mcg ethinyl estradiol. Researchers aimed to determine the serum protein binding traits of both progestins and their pharmacokinetics. They used specific radioimmunoassays and ultrafiltration to measure levels and serum protein binding of gestodene and the active metabolite of desogestrel, 3-keto-desogestrel (KDG). The free faction of both progestins was the same 91.9% for gestodene and 1.7% for KDG). The percent gestodene bound to albumin was not significantly different from that of KDG (47.8% vs. 63.7%). Similarly there was no significant difference between the percent gestodene and percent KDG bound to sex hormone binding globulin (SHBG) while gestodene tended to bind more with SHBG than albumin. The SHBG binding of gestodene was not as strong as that of albumin binding of KDG, however. After pill administration, KDG reached maximum levels later than did gestodene (1.5 hours vs. 7 hours). Mean maximum level of gestodene was 4.9 ng/ml. Post maximum levels of gestodene fell biphasically with half lives at a mean of 0.13 hours and 14.7 hours, respectively. The area under the cure of gestodene was 32.9 ng x ml-1 x h. Mean maximum level of KDg was 1.7 ng/ml. Post-maximum levels of gestodene fell biphasically with half lives at a mean of 0.5 and 17 hours, respectively. The area under the curve of gestodene was 15.2 ng x ml-1 x h. Lower bioavailability of KDG (60-80% vs. 100% for gestodene) may have accounted for the slightly greater interindividual variation of drug levels for KDG than gestodene.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Blood Proteins / metabolism
  • Contraceptives, Oral / pharmacokinetics*
  • Desogestrel / blood
  • Desogestrel / pharmacokinetics*
  • Half-Life
  • Humans
  • Male
  • Norpregnenes / blood
  • Norpregnenes / pharmacokinetics*
  • Protein Binding
  • Radioimmunoassay


  • Blood Proteins
  • Contraceptives, Oral
  • Norpregnenes
  • Gestodene
  • etonogestrel
  • Desogestrel