Bodor N, Loftsson T, Wu W M
Center for Drug Discovery, J. Hillis Miller Health Center, College of Pharmacy, University of Florida, Gainesville 32606.
Pharm Res. 1992 Oct;9(10):1275-8. doi: 10.1023/a:1015849132396.
The soft corticosteroid, loteprednol etabonate (chloromethyl 17 alpha-ethoxycarbonyloxy-11 beta-hydroxy-3-oxoandrosta-1,4-diene-17 beta-carboxylate), I, was designed based on the "inactive metabolite approach." Accordingly, I should be metabolized by hydrolysis to the corresponding inactive cortienic acid derivative, II. The in vitro and in vivo metabolism of I indeed yielded mainly this inactive metabolite, which is more hydrophilic and thus readily eliminated from the body. Relatively high levels of I were found in tissues after intravenous administration of the drug in rats. The permeability of I through hairless mouse skin was comparable to what has been found for related "hard" steroids, without significant metabolism taking place in the skin.
软质皮质类固醇卤倍他索丙酸酯（17α - 乙氧基羰基氧基 - 11β - 羟基 - 3 - 氧代雄甾 - 1,4 - 二烯 - 17β - 羧酸氯甲酯），即化合物I，是基于“无活性代谢物方法”设计的。因此，化合物I应通过水解代谢为相应的无活性皮质酸衍生物，即化合物II。化合物I的体外和体内代谢确实主要产生了这种无活性代谢物，该代谢物亲水性更强，因此易于从体内消除。在大鼠静脉注射该药物后，在组织中发现了相对较高水平的化合物I。化合物I透过无毛小鼠皮肤的渗透性与相关“硬质”类固醇相当，且在皮肤中未发生显著代谢。
