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 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.
Bodor
N
N
Center for Drug Discovery, J. Hillis Miller Health Center, College of Pharmacy, University of Florida, Gainesville 32606.
Loftsson
T
T
Wu
W M
WM
D000730:Androstadienes / Q000493:pharmacokinetics*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D000069559:Loteprednol Etabonate; D008297:Male; D051379:Mice; D008812:Mice, Hairless; D051381:Rats; D017207:Rats, Sprague-Dawley; D012869:Skin Absorption; D014018:Tissue Distribution
D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D000069559:Loteprednol Etabonate