Metabolism, distribution, and transdermal permeation of a soft corticosteroid, loteprednol etabonate

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 inactiv...

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Bibliographic Details
Published inPharmaceutical research Vol. 9; no. 10; p. 1275
Main Authors Bodor, N, Loftsson, T, Wu, W M
Format Journal Article
LanguageEnglish
Published United States 01.10.1992
Subjects
Androstadienes - pharmacokinetics
Animals
Anti-Inflammatory Agents - pharmacokinetics
Chromatography, High Pressure Liquid
In Vitro Techniques
Loteprednol Etabonate
Male
Mice
Mice, Hairless
Rats
Rats, Sprague-Dawley
Skin Absorption
Tissue Distribution
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Summary: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.
ISSN:0724-8741
DOI:10.1023/A:1015849132396