Dose- and time-dependent changes in blood and adrenal levels of multiple steroids in rats after administration of ketoconazole with or without ACTH.

Dose- and time-dependent changes in blood and adrenal levels of multiple steroids in rats after administration of ketoconazole with or without ACTH. J Toxicol Sci. 2019;44(9):601-610 Authors: Tochitani T, Yamashita A, Matsumoto I, Kouchi M, Fujii Y, Miyawaki I Abstract To verify simultaneous measurement of blood levels of adrenal steroids as a tool to evaluate drug effects on adrenal steroidogenesis, dose- and time-dependent changes in blood levels of corticosterone and its precursors (pregnenolone, progesterone and deoxycorticosterone), as well as their relationship with the pathological changes in the adrenal gland, were examined in rats dosed with ketoconazole (KET). Also examined were whether effects on adrenal steroidogenesis that were not obvious in the blood steroid levels after sole administration of KET could be revealed by post-administration of ACTH, and the correlation between the blood and adrenal steroid levels. Male rats were dosed with 15, 50, or 150 mg/kg of KET for 1 or 7 days with or without ACTH, and the blood and adrenal concentrations of the steroids were measured. KET increased the blood deoxycorticosterone level even at a dose level and time point at which histopathological changes were not obvious. KET-induced changes in blood levels of other steroids were revealed by ACTH, and the blood and adrenal levels were generally correlated especially after ACTH post-administration. Thus, blood levels of adrenal stero...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research