泼尼松 ADME
中文名称
通路描述
泼尼松（PREDN）是泼尼松龙（PREDL）的前药，吸收迅速。为了达到对几乎不溶于水分子的最高摄取，最高剂量 50 mg 必须溶解在 250 ml 水中。其在肝细胞中转化为高度活性的泼尼松龙（PREDL）是可逆的，但代表 favored 反应方向（Pickup, 1979）。泼尼松和泼尼松龙被认为在临床上完全等效。避免通过直接给予泼尼松龙来避免高 GI 浓度的理论优势从未被证明具有临床相关性（Vogt 等，2007）。仅 2-5% 的给定泼尼松剂量以未改变形式在尿液中排泄。氢化生成泼尼松龙后至少形成 20 种代谢物及其共轭物并排泄。全身和局部使用的主要代谢物是 20α-和 20β-去氢泼尼松，以及 20α-和 20β-去氢泼尼松龙（20AH-PREDN, 20BH-PREDN, 20AH-PREDL, 20BH-PREDL），此外还有 6β-羟基化合物 6B-OH-PREDN 和 6B-OH-PREDL（Matabosch 等，2015; Mazzarino 等，2019）。PREDN 的氢化和 PREDL 的去氢化是互补反应，在不同细胞类型中占主导地位。而肝脏和脂肪细胞将 PREDN 转化为 PREDL，结肠和肾脏细胞部分将 PREDL 转化回 PREDN（Jamieson 等，1995; Ricketts 等，1998; Diederichs 等，2002）。我们在图中通过展示肝细胞和肾脏细胞中的示例反应来描绘这种平衡。
英文描述
Prednisone ADME Prednisone (PREDN) is a prodrug of prednisolone (PREDL), and is rapidly absorbed. To achieve high uptake of the near water-insoluble molecule the highest dose 50 mg has to be dissolved in 250 ml water. Its conversion to the highly active prednisolone (PREDL) in liver cells is reversible but represents the favored reaction direction (Pickup, 1979).
Prednisone and prednisolone are considered to be fully therapeutically equivalent. The theoretical advantage of avoiding high GI concentrations of prednisone by administering prednisolone directly has never been shown to be clinically relevant (Vogt et al, 2007).
Only 2â5% of a given dose of prednisone is excreted unchanged in urine. After hydrogenation to prednisolone at least 20 metabolites and their conjugates are formed and excreted. The main metabolites both after systemic and topical use are 20alpha- and 20beta-dihydro-prednisone, as well as 20alpha- and 20beta-dihydro-prednisolone (20AH-PREDN, 20BH-PREDN, 20AH-PREDL, 20BH-PREDL), in addition to the 6beta-hydroxy compounds 6B-OH-PREDN and 6B-OH-PREDL (Matabosch et al, 2015; Mazzarino et al, 2019). Hydrogenation of PREDN and dehydrogenation of PREDL are complementary reactions that are dominant in different cell types. While liver and fat cells convert PREDN to PREDL, colon and kidney cells partly convert PREDL back to PREDN (Jamieson et al, 1995; Ricketts et al, 1998; Diederichs et al, 2002). We have depicted this equilibrium by showing example reactions in hepatocytes and kidney cells in the diagram.
Prednisone and prednisolone are considered to be fully therapeutically equivalent. The theoretical advantage of avoiding high GI concentrations of prednisone by administering prednisolone directly has never been shown to be clinically relevant (Vogt et al, 2007).
Only 2â5% of a given dose of prednisone is excreted unchanged in urine. After hydrogenation to prednisolone at least 20 metabolites and their conjugates are formed and excreted. The main metabolites both after systemic and topical use are 20alpha- and 20beta-dihydro-prednisone, as well as 20alpha- and 20beta-dihydro-prednisolone (20AH-PREDN, 20BH-PREDN, 20AH-PREDL, 20BH-PREDL), in addition to the 6beta-hydroxy compounds 6B-OH-PREDN and 6B-OH-PREDL (Matabosch et al, 2015; Mazzarino et al, 2019). Hydrogenation of PREDN and dehydrogenation of PREDL are complementary reactions that are dominant in different cell types. While liver and fat cells convert PREDN to PREDL, colon and kidney cells partly convert PREDL back to PREDN (Jamieson et al, 1995; Ricketts et al, 1998; Diederichs et al, 2002). We have depicted this equilibrium by showing example reactions in hepatocytes and kidney cells in the diagram.
所含基因
10 个基因