title: The effects of delta1-cortienic acid on skin blanching, pharmacokinetics and stability of loteprednol etabonate.
abstract: The effect of delta1-cortienic acid (delta1-CA) on human skin blanching activity of the soft corticosteroid, loteprednol etabonate (LE), has been studied. Ten volunteers had applied to their forearms a dose of LE ranging from 0.1 to 1 mM, or LE from 0.1 to 1 mM in combination with 2-times the concentration of delta1-CA (0.2 - 2mM). The results indicate that delta1-CA increased LE's effect on human vasoconstriction/skin blanching activity, both in the intensity and duration. This enhancing effect of delta1-CA was also observed in other blanching studies with other corticosteroids, such as hydrocortisone. The enhancement may occur through the displacement of LE bound to transcortin (also known as corticosteroid-binding globulin, or CBG) by delta1-CA as delta1-CA has a higher affinity for CBG than that for glucocorticoid receptor (GR), resulting in more free-LE to act on GR, and increased skin blanching. In rat studies, intravenous injection of delta1-CA (5-50 mg/kg) did not affect the pharmacokinetics of LE (5 mg/kg), indicating that delta1-CA is safe for combined use with LE. In stability studies, the presence of delta1-CA at the same concentrations as LE in aqueous suspension (0.1 and 0.2%) significantly increased the stability of LE. Thus, the combination of delta1-CA with LE serves an enhancing and stabilizing role while not impacting the pharmacokinetic properties of LE.
authors: Center for Drug Discovery, College of Pharmacy, University of Florida, Gainesville 32610-0497, USA.
authors: W M
authors: WM
authors: Wu
authors: E T
authors: ET
authors: Bodor
authors: J
authors: J
authors: Howes
authors: N
authors: N
authors: Bodor
mesh_terms: D000293:Adolescent; D000328:Adult; D000730:Androstadienes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D005542:Forearm / Q000098:blood supply; D006801:Humans; D006854:Hydrocortisone / Q000494:pharmacology; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D000069559:Loteprednol Etabonate; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply*; D013056:Spectrophotometry, Ultraviolet; D013535:Suspensions; D014661:Vasoconstriction / Q000187:drug effects; D055815:Young Adult
chemical_list: D000730:Androstadienes; D000893:Anti-Inflammatory Agents; D007202:Indicators and Reagents; D013535:Suspensions; C527981:delta1-cortienic acid; D006854:Hydrocortisone; D000069559:Loteprednol Etabonate