SERUM DISTRIBUTION OF 2 CONTRACEPTIVE PROGESTINS - 3-KETODESOGESTREL AND GESTODENE

A cross-over study of two oral contraceptive formulations, containing 30 mu g ethinylestradiol in combination with 150 mu g desogestrel (Mar velon(R)) or 75 mu g gestodene (Femovan(R)), has been performed to com pare the serum distribution and pharmacokinetics of gestodene and the active metabolite of desogestrel, namely 3-ketodesogestrel. Serum conc entrations of both sex hormone-binding globulin (SHBG) and corticoster oid-binding globulin (CBG) were also measured and were increased more than 3-fold and 2-fold, respectively, on day 21 of the treatment cycle , with no statistically significant difference between treatment group s. in addition, 35 days after ingestion of either oral contraceptive h ad ceased, the serum SHBG and CBG concentrations were similar to the p retreatment values. During treatment cycles, increased serum SHBG leve ls were associated with a redistribution of 3-ketodesogestrel and gest odene such that the non-protein-bound (NPB) and albumin-bound fraction s were reduced in concert with an increase in the relative proportions bound to SHBG. The proportion of gestodene bound to SHBG was consiste ntly higher than that observed for 3-ketodesogestrel, and this undoubt edly reflects the higher affinity of SHBG for gestodene (K-d=1.2 nM at 37 degrees C) when compared to 3-ketodesogestrel (K-d=4.7 nM at 37 de grees C). It also probably accounts, in part, for the much higher tota l serum levels of gestodene (8.58 nmol/L) when compared to 3-ketodesog estrel (2.37 nmol/L) during the treatment cycles. Consequently, the ab solute amounts of NPB, non-SHBG-bound, and SHBG-bound gestodene are si gnificantly higher than those measured for S-ketodesogestrel. It is co ncluded that ethinylestradiol-induced increases in serum SHBG levels d uring treatment with Marvelon(R) or Femovan(R), influenced the distrib ution and total amount of 3-ketodesogestrel and gestodene in serum, re spectively, and that this, combined with the higher affinity of SHBG f or gestodene, results in a greater amount of bioavailable gestodene co mpared to 3-ketodesogestrel, despite the smaller dose of gestodene adm inistered.