Premium
The selective glucocorticoid receptor agonist mapracorat displays a favourable safety–efficacy ratio for the topical treatment of inflammatory skin diseases in dogs
Author(s) -
Bäumer Wolfgang,
Rossbach Kristine,
Schmidt Bernard H.
Publication year - 2017
Publication title -
veterinary dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.744
H-Index - 60
eISSN - 1365-3164
pISSN - 0959-4493
DOI - 10.1111/vde.12315
Subject(s) - triamcinolone acetonide , medicine , peripheral blood mononuclear cell , agonist , pharmacology , glucocorticoid , corticosteroid , in vivo , glucocorticoid receptor , tumor necrosis factor alpha , endocrinology , receptor , immunology , chemistry , in vitro , biology , biochemistry , microbiology and biotechnology
Background Mapracorat is a nonsteroidal Selective Glucocorticoid Receptor Agonist ( SEGRA ) that is presumed to have a better therapeutic index compared to classical glucocorticoids. Objectives To compare the efficacy and safety of mapracorat with classical glucocorticoids used for the treatment of allergic skin diseases in dogs. Animals Six laboratory beagles. Methods The effect of mapracorat on lipopolysaccharide‐induced TNF α 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 TNF α secretion from activated canine PBMC with a half maximal inhibitory concentration ( IC 50 ) 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. Conclusion 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 SEGRA s show promise in the management of inflammatory and pruritic skin diseases in dogs.