Brain permeability of inhaled corticosteroids

• DOI: 10.1211/jpp.57.9.0010
• Publication Date: 2005-08-04T22:50:15Z
• Authors: Vikram Arya; Manish Issar; Yaning Wang; Guenther Hochhaus; James D Talton
• Keywords: P-glycoprotein

Abstract The aim of this study was to evaluate if the permeability inhaled corticosteroids entering brain is reduced and P-glycoprotein (P-gp) transporters are involved. Currently employed were given intravenously intratracheally rats at a dose 100 μg kg−1. An ex-vivo receptor binding assay used monitor over 12 h glucocorticoid occupancy in systemic reference organ (kidney). involvement P-gp triamcinolone acetonide assessed wild-type mice mdr1a(-/-) knockout (mice lacking gene for expressing P-gp). After both forms administration, average occupancies 20–56% those organ, with more lipophilic drugs showing pronounced occupation. While liver similar after administration acetonide, significantly greater (mdr1a(-/-): 47.6%, 40.2–55.0%, n = 2; wild-type: 11.5±33.0%, 3). Penetration into (especially lower lipophilicity) reduced. Experiments confirmed transporters. Further studies needed assess whether potential drug interactions transporter level pharmacological significance.