title: Ex vivo absorption of promestriene from oil-in-water emulsion into infant foreskin.
abstract: Hypospadias is a birth defect in which the urinary tract opening is not at the tip of the penis. Hypospadias surgery is frequently complicated by healing deficiencies. Topical treatments with oestrogens were reported to improve healing. In the present study, ex vivo percutaneous absorption of promestriene, a synthetic oestrogen resulting of the double esterification of estradiol was conducted as a pre-requisite for further clinical trial in infants. Penetration of promestriene into infant foreskin treated with commercial oil in water emulsion (10 μg mg(-1)) for 24 h was characterized showing controlled release properties enabling epidermal concentration more than six times higher than dermal concentration (4.13±2.46 mg g(-1) versus 0.62±0.84 mg g(-1), respectively). Furthermore, apparent promestriene fluxes into and through the skin (i.e., 1.5 μg cm(-2) h(-1) and<0.89 μg cm(-2) h(-1), respectively) were calculated from (i) drug amount retained into epidermis and dermis, or (ii) the limit of detection into the receptor fluid. In conclusion, less than 2% of initial dose were absorbed within 24h which compared well with others steroids applied topically in colloidal systems.
authors: Service Pharmaceutique, Plateforme FRIPHARM, Groupement Hospitalier Edouard Herriot, Hospices Civils de Lyon, 5 Place d'Arsonval, F-69437 Lyon Cedex 03, France; Laboratoire de Pharmacie Galénique Industrielle, EA 4169 Fonctions Physiologiques et Pathologiques de la Barrière Cutanée, Plateforme FRIPHARM, Université Claude Bernard Lyon 1, 8 Avenue Rockefeller, F-69373 Lyon Cedex 08, France. Electronic address: damien.salmon01@chu-lyon.fr.
authors: D
authors: D
authors: Salmon
authors: B
authors: B
authors: Kassai
authors: L
authors: L
authors: Roussel
authors: P
authors: P
authors: Mouriquand
authors: C
authors: C
authors: Gérard
authors: D B
authors: DB
authors: Gorduza
authors: C
authors: C
authors: Serre
authors: F
authors: F
authors: Falson
authors: C
authors: C
authors: Pivot
authors: F
authors: F
authors: Pirot
mesh_terms: D004655:Emulsions; D004958:Estradiol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D004967:Estrogens / Q000737:chemistry / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry; D052816:Foreskin / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D009821:Oils / Q000737:chemistry; D012869:Skin Absorption; D014867:Water / Q000737:chemistry
chemical_list: D004655:Emulsions; D004967:Estrogens; D005079:Excipients; D009821:Oils; D014867:Water; D004958:Estradiol; C013657:promestriene
keywords: Human foreskin; Percutaneous absorption; Promestriene; Steroid