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- W2153368089 abstract "Prednisolone (5 mg/kg intravenous) was administered to adrenalectomized male and female Sprague‐Dawley rats (250–350 g) to assess the effects of gender on disposition and pharmacoim‐munodynamics. Plasma concentrations of prednisolone were determined by high‐performance liquid chromatography. Incorporation of [3H]thymidine (3H‐TDR) was used to determine whole blood T‐cell (WBTC) trafficking and deactivation following stimulation with Con‐canavalin‐A. Whole blood T‐cell trafficking was determined indirectly by using the glucocorticoid receptor antagonist RU‐40555 (250 ng/mL) added to ex vivo cultures of whole blood from animals dosed with prednisolone. Mean ( ± SD) prednisolone clearance values were 3.22 ± 0.88 and 3.46 ± 0.96 L/h/kg in males and females, respectively. After administration of prednisolone, relative T‐cell counts decreased slowly with time to reach a nadir at 3–5 h and returned to baseline levels by 8 h. Fitting data using an indirect response model yielded mean prednisolone 50% inhibitory concentration for inhibition of WBTC trafficking (IC50T) that was lower in males compared with females (0.14 ± 0.16 versus 1.03 ± 0.06 ng/mL; p < 0.05). In the absence of RU‐40555, an immediate and complete inhibition of 3H‐TDR incorporation into WBTC was observed (deactivation) and baseline levels were recovered slowly as prednisolone was cleared from blood. The mean 50% inhibitory concentration for inhibition of WBTC deactivation (IC50D) based on an inhibitory Imax model was similar in males and females (0.20 ± 0.24 versus 0.18 ± 0.12 ng/mL). Although male and female rats have similar exposure to prednisolone after 5‐mg/kg doses, males are more sensitive to the inhibition of WBTC trafficking, whereas no gender effects on deactivation of WBTC exist." @default.
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- W2153368089 title "Influence of Gender on Prednisolone Effects on Whole Blood T-Cell Deactivation and Trafficking in Rats" @default.
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- W2153368089 doi "https://doi.org/10.1021/js9802695" @default.
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