title: The selective glucocorticoid receptor agonist mapracorat displays a favourable safety-efficacy ratio for the topical treatment of inflammatory skin diseases in dogs.
abstract: BACKGROUND
  Mapracorat is a nonsteroidal Selective Glucocorticoid Receptor Agonist (SEGRA) that is presumed to have a better therapeutic index compared to classical glucocorticoids.
  
  
  OBJECTIVE
  To compare the efficacy and safety of mapracorat with classical glucocorticoids used for the treatment of allergic skin diseases in dogs.
  
  
  METHODS
  Six laboratory beagles.
  
  
  METHODS
  The effect of mapracorat on lipopolysaccharide-induced TNFα secretion from canine peripheral blood derived mononuclear cells (PBMC) was tested. In vivo, mapracorat was compared to triamcinolone acetonide using a skin inflammation model. Skin fold thickness was determined after daily administration of mapracorat and triamcinolone acetonide over 14 days.
  
  
  RESULTS
  Mapracorat concentration dependently inhibited TNFα secretion from activated canine PBMC with a half maximal inhibitory concentration (IC50) value of approximately 0.2 nmol/L. Intradermal injection of compound 48/80 (50 μg in 50 μL saline) resulted in a clear wheal and flare reaction over the 60 min observation period. Topical pre-treatment with mapracorat (0.1%) and triamcinolone acetonide (0.015%) led to significant reduction in the wheal and flare responses compared to vehicle (acetone) treated areas. However, once daily topical administration of triamcinolone acetonide significantly reduced skin fold thickness from day 8 to 14, whereas no such reduction was observed for mapracorat.
  
  
  CONCLUSIONS
  These results demonstrate that mapracorat has comparable anti-inflammatory efficacy to classical steroidal glucocorticoids under these experimental settings and maintenance of skin fold thickness indicates a better safety profile compared to triamcinolone acetonide at equipotent concentrations. This profile further suggests that SEGRAs show promise in the management of inflammatory and pruritic skin diseases in dogs.
authors.affiliation: Department of Molecular Biomedical Sciences, College of Veterinary Medicine, NC State University, 1060 William Moore Drive, Raleigh, NC, 27607, USA.|Institute of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, Hannover, 30559, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumer
authors.affiliation: Institute of Pharmacology, Toxicology and Pharmacy, University of Veterinary Medicine Hannover, Bünteweg 17, Hannover, 30559, Germany.
authors.forename: Kristine
authors.initials: K
authors.lastname: Rossbach
authors.affiliation: Bayer Animal Health GmbH, Leverkusen, 51373, Germany.
authors.forename: Bernard H
authors.initials: BH
authors.lastname: Schmidt
mesh_terms: D000287:Administration, Topical; D000818:Animals; D001572:Benzofurans / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D003872:Dermatitis / Q000188:drug therapy / Q000662:veterinary*; D003879:Dermatologic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004283:Dog Diseases / Q000188:drug therapy*; D004285:Dogs; D005260:Female; D008297:Male; D000439:Pentanols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D011965:Receptors, Glucocorticoid / Q000819:agonists*; D016896:Treatment Outcome; D014222:Triamcinolone Acetonide / Q000008:administration & dosage / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
chemical_list: D001572:Benzofurans; D003879:Dermatologic Agents; D000439:Pentanols; D011804:Quinolines; C546413:R-1,1,1-trifluoro-4-(5-fluoro-2,3-dihydrobenzofuran-7-yl)-4-methyl-2-(((2-methyl-5-quinolyl)amino)methyl)pentan-2-ol; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D014222:Triamcinolone Acetonide