Tissue Distribution of Sex Steroids: Concentration of 17β‐Oestradiol and Cyproterone Acetate in Selected Organs of Female Wistar Rats

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Abstract
The tissue distribution of 17β‐oeslradiol and cyproterone acetate was investigated after intravenous and intragastric administration to female Wistar rats by measuring the time course of the concentration of the sex steroids in plasma, liver, kidney, brain, and heart by radioimmunoassay. Test substances were administered intravenously in doses of 0.1 mg/kg each and intragastrically in doses of 10 mg/kg (17β‐oestradiol) and 0.1 mg/kg (cyproterone acetate) corresponding to the expected oral bioavailability. Tissue distribution was assessed within each mode of administration by AUCorgan/ AUCplasma‐quotients (Q‐values), and between both routes of administration by F‐values representing (bio‐ and organ availability) and R‐values, which express the organ load after intragastric compared to intravenous administration if the same amount of drug has been made bioavailable in the plasma after both routes (for explanation see next page). The absolute bioavailability of 17β‐oestradiol after intragastric administration of 10 mg/kg was ca. 8%. The oestradiol liver load after intragastric administration was about 20 times higher than after intravenous administration, whereas the drug load of other organs was independent of the administration route. Cyproterone acetate was completely bioavailable after intragastric administration in a dose of 0.1 mg/kg. Cyproterone acetate levels and AUC‐values in all organs investigated were higher when compared to the plasma with highest levels in the liver. The organ distribution of cyproterone acetate including the drug liver load was independent of the route of administration.