Contrary to adult, neonatal rats show pronounced brain uptake of corticosteroids

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Vikram AryaG Hochhaus

Abstract

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 microg/kg and to adult rats at 100 microg/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 microg/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 microg/kg triamcinolone acetonide to adult rats, receptor occupancies in the brain were significantly lower (brain/liver ratio, 0.21 +/- 0.14; p < 0.001...Continue Reading

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Citations

Sep 17, 2009·Acta Neuropathologica·Beatriz Gómez-González, Alfonso Escobar
Jul 11, 2012·Neuropharmacology·Carolina García-BarrosoAna García-Osta
Mar 31, 2010·Regulatory Toxicology and Pharmacology : RTP·Paul Baldrick
Jul 22, 2018·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jill M GoldsteinRobert J Handa
Apr 18, 2019·The AAPS Journal·Syedsaoud ZaidiGünther Hochhaus
Nov 12, 2015·PloS One·Sudhir P DeosarkarMohammad F Kiani
Dec 14, 2018·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Tanzir B MortuzaJames V Bruckner

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