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- Title
Brain permeability of inhaled corticosteroids.
- Authors
Vikram Arya; Manish Issar; Yaning Wang; James D. Talton; Guenther Hochhaus
- Abstract
The aim of this study was to evaluate if the permeability of inhaled corticosteroids entering the brain is reduced and if P-glycoprotein (P-gp) transporters are involved. Currently employed inhaled corticosteroids were given intravenously and intratracheally to rats at a dose of 100 μg kg−1. An ex-vivo receptor binding assay was used to monitor over 12 h the glucocorticoid receptor occupancy in the brain and a systemic reference organ (kidney). The involvement of P-gp in the brain permeability of triamcinolone acetonide was assessed in wild-type mice and mdr1a(−/−) knockout mice (mice lacking the gene for expressing P-gp). After both forms of administration, the average brain receptor occupancies were 20–56% of those of the reference organ, with the more lipophilic drugs showing a more pronounced receptor occupation. While the receptor occupancies in the liver of wild-type and mdr1a(−/−) mice were similar after administration of triamcinolone acetonide, brain receptor occupancies in mdr1a(−/−) mice were significantly greater (mdr1a(−/−): 47.6%, 40.2–55.0%, n = 14; 2; wild-type: 11.5 ± 33.0%, n = 14; 3). Penetration into the brain for inhaled corticosteroids (especially those of lower lipophilicity) is reduced. Experiments in mdr1a(−/−) mice confirmed the involvement of P-gp transporters. Further studies are needed to assess whether potential drug interactions at the transporter level are of pharmacological significance.
- Publication
Journal of Pharmacy & Pharmacology, 2005, Vol 57, Issue 9, p1159
- ISSN
0022-3573
- Publication type
Article