DMD Large equally mixed donor pool

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

Drug Metabolism and Disposition Fast Forward
First published on February 28, 2006; DOI: 10.1124/dmd.105.007419

0090-9556/06/3406-939-942$20.00
DMD 34:939-942, 2006

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dmd.105.007419v1
34/6/939    most recent
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Arya, V.
Right arrow Articles by Hochhaus, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Arya, V.
Right arrow Articles by Hochhaus, G.

CONTRARY TO ADULT, NEONATAL RATS SHOW PRONOUNCED BRAIN UPTAKE OF CORTICOSTEROIDS

Vikram Arya, Vincent G. Demarco, Manish Issar1, and Günther Hochhaus

Department of Pharmaceutics, College of Pharmacy, University of Florida, Gainesville, Florida (V.A., M.I., G.H.); and Department of Child Health, School of Medicine, University of Missouri, Columbia, Missouri (V.G.D.)

Neurotoxic adverse effects after systemic corticosteroid administration are elevated in preterm infants. To test whether this might be related to an immature blood-brain barrier (BBB) that permits corticosteroids to enter the brain and induce neurotoxic effects, this study assessed the differences in brain permeability of triamcinolone acetonide after intratracheal administration to neonatal (10- to 11-day-old) and adult rats. Triamcinolone acetonide (or the phosphate prodrug in the case of neonatal rats) was administered intratracheally to neonatal rats at doses of 2.5, 25, or 50 µg/kg and to adult rats at 100 µg/kg. An ex vivo receptor binding assay was used to monitor the cumulative brain and liver glucocorticoid receptor occupancies over 6 h. Brain and liver receptor occupancies in neonates were similar for the 25 and 50 µg/kg triamcinolone acetonide phosphate (brain/liver receptor occupancy ratio, 1.10 ± 0.14 and 0.87 ± 0.13, respectively), whereas some reduction in the brain permeability was seen at the lower dose. After intratracheal administration of 100 µg/kg triamcinolone acetonide to adult rats, receptor occupancies in the brain were significantly lower (brain/liver ratio, 0.21 ± 0.14; p < 0.001). The study demonstrated that glucocorticoids enter the brain of neonatal rats because of an immature BBB. The results of this study support the hypothesis that neurotoxic adverse effects in preterm infants after systemic corticosteroid administration might be related to an immature BBB.

Address correspondence to: Dr. Guenther Hochhaus, P.O. Box 100494, Department of Pharmaceutics, College of Pharmacy, JHMHC, University of Florida, Gainesville, FL 32610. E-mail: hochhaus{at}ufl.edu






Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 2006 by the American Society for Pharmacology and Experimental Therapeutics.