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Brain permeability of inhaled corticosteroids
Vikram Arya1, Manish Issar, Yaning Wang
1Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, FL 32610, USA.
The Journal of Pharmacy and Pharmacology
|August 18, 2005
Summary
Inhaled corticosteroids show reduced brain penetration, particularly less lipophilic ones. P-glycoprotein (P-gp) transporters are confirmed to be involved in limiting brain entry of these important medications.
Area of Science:
- Pharmacology
- Neuroscience
- Drug Delivery
Background:
- Inhaled corticosteroids (ICS) are widely used for respiratory conditions.
- Understanding their brain penetration is crucial for assessing potential central nervous system effects.
- P-glycoprotein (P-gp) is a known efflux transporter that can limit drug entry into the brain.
Purpose of the Study:
- To determine if brain permeability of ICS is reduced.
- To investigate the role of P-glycoprotein (P-gp) transporters in ICS brain entry.
Main Methods:
- Rats received ICS intravenously and intratracheally.
- Glucocorticoid receptor occupancy in the brain and kidney was measured over 12 hours using an ex-vivo assay.
- Triamcinolone acetonide brain permeability was assessed in wild-type and P-gp knockout mice (mdr1a(-/-)).
Main Results:
- ICS brain receptor occupancy was 20-56% of kidney occupancy, with higher lipophilicity correlating with greater brain occupation.
- In mdr1a(-/-) mice, brain receptor occupancy for triamcinolone acetonide was significantly higher than in wild-type mice.
- These findings confirm P-gp transporter involvement in limiting ICS brain penetration.
Conclusions:
- Inhaled corticosteroids exhibit reduced penetration into the brain, especially those with lower lipophilicity.
- P-glycoprotein transporters play a significant role in restricting the brain entry of ICS.
- Further research is needed to evaluate the clinical significance of P-gp interactions with ICS.