title: Enhanced Activity of Topical Hydrocortisone by Competitive Binding of Corticosteroid-Binding Globulin.
abstract: Atopic dermatitis of sensitive areas such as the face, particularly in children, is a difficult disease to treat as the standard therapeutic, topical steroids, is contraindicated for this application in children. Hydrocortisone (HC) can be used in these instances because it has been shown to be safe, but is often ineffective as it is a relatively weak steroid, especially at over-the-counter concentrations. To enhance the local topical activity of HC, the terminal inactive metabolite of prednisolone, Δ(1)-cortienic acid (Δ(1)-CA), is added to HC, as Δ(1)-CA preferentially binds transcortin, liberating more HC to elicit its therapeutic effect. Skin blanching studies, which are used to evaluate the potency of topical steroids, were employed to assess the ability of Δ(1)-CA to enhance the activity of HC. The results demonstrate that Δ(1)-CA, when applied in combination with HC, does indeed potentiate the vasoconstriction effect of topically applied HC, while having no effect alone. Thus, addition of the inert prednisolone metabolite Δ(1)-CA can increase the therapeutic effect of over-the-counter concentrations of HC when applied topically.
authors.affiliation: Bodor Laboratories, Inc., 4400 Biscayne Blvd, Suite 980, Miami, Florida 33137. Electronic address: etbodor@bodorlabs.com.
authors.forename: Erik T
authors.initials: ET
authors.lastname: Bodor
authors.affiliation: Bodor Laboratories, Inc., 4400 Biscayne Blvd, Suite 980, Miami, Florida 33137.
authors.forename: Whei-Mei
authors.initials: WM
authors.lastname: Wu
authors.affiliation: Signature R&D Holdings, LLC, 1415 Stinson Road, Allen, Texas 75002.
authors.forename: V Ravi
authors.initials: VR
authors.lastname: Chandran
authors.affiliation: Bodor Laboratories, Inc., 4400 Biscayne Blvd, Suite 980, Miami, Florida 33137.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Bodor
mesh_terms: D000279:Administration, Cutaneous; D000287:Administration, Topical; D001667:Binding, Competitive; D005542:Forearm; D006801:Humans; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology*; D004366:Nonprescription Drugs; D011239:Prednisolone / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D012039:Regional Blood Flow / Q000187:drug effects; D012867:Skin / Q000098:blood supply / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects; D014156:Transcortin / Q000737:chemistry / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D004366:Nonprescription Drugs; D014156:Transcortin; D011239:Prednisolone; D006854:Hydrocortisone
keywords: drug design; drug transport; metabolism; protein binding; stability; transdermal