TISSUE DISTRIBUTION OF SEX STEROIDS - CONCENTRATION OF 17-BETA-ESTRADIOL AND CYPROTERONE-ACETATE IN SELECTED ORGANS OF FEMALE WISTAR RATS

The tissue distribution of 17 beta-oestradiol and cyproterone acetate was investigated after intravenous and intragastric administration to female Wistar rats by measuring the time course of the concentration o f the sex steroids in plasma, liver, kidney, brain, and heart by radio immunoassay. Test substances were administered intravenously in doses of 0.1 mg/kg each and intragastrically in doses of 10 mg/kg (17 beta-o estradiol) and 0.1 mg/kg (cyproterone acetate) corresponding to the ex pected oral bioavailability. Tissue distribution was assessed within e ach mode of administration by AUC(organ)/AUC(plasma)-quotients (Q-valu es), and between both routes of administration by F-values representin g (bio-and organ availability) and R-values, which express the organ l oad after intragastric compared to intravenous administration if the s ame amount of drug has been made bioavailable in the plasma after both routes (for explanation see next page). The absolute bioavailability of 17 beta-oestradiol after intragastric administration of 10 mg/kg wa s ca. 8%. The oestradiol liver load after intragastric administration was about 20 times higher than after intravenous administration, where as the drug load of other organs was independent of the administration route. Cyproterone acetate was completely bioavailable after intragas tric administration in a dose of 0.1 mg/kg. Cyproterone acetate levels and AUG-values in all organs investigated were higher when compared t o the plasma with highest levels in the liver. The organ distribution of cyproterone acetate including the drug liver load was independent o f the route of administration.