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Permeability of the developing and mature blood-brain barriers to the theophylline in rats
journal contribution
posted on 2023-05-16, 11:09 authored by Habgood, MD, Knott, GW, Dziegielewska, KM, Norman SaundersNorman Saunders1. In the present study, the uptake of theophylline and L-glucose into the adult and neonatal rat brain has been investigated. Steady state cerebrospinal fluid (CSF) and brain concentrations of theophylline were reached within 1 h following a single intraperitonenl (i.p.) injection, whereas steady state CSF and brain concentrations of L-glucose were not approached until after 5 h. 2. Steady state brain:plasma and CSF:plasma concentration ratios for theophylline and L-glucose in neonatal rats were significantly higher than ratios in adult rats. Erythrocyte:plasma ratios for theophylline in neonatal rats were also significantly higher than ratios in adult rats. Steady state ratios for theophylline were significantly higher than those for L-glucose in both neonatal and adult rats. 3. Respiratory acidosis (pH 6.9-7.0) did not affect steady state CSF:plasma or brain:plasma ratios for theophylline in neonatal or adult rats. In contrast, steady state CSF:plasma and brain:plasma ratios for L-glucose were increased by respiratory acidosis. 4. The lower steady state CSF:plasma, brain:plasma and erythrocyte:plasma ratios for theophylline in adult rats are likely to be due to a higher concentration of plasma proteins in adult blood compared with neonates, with a greater retention of protein-bound (non-exchangeable) theophylline in adult blood, and are unlikely to be due to p-glycoprotein-mediated efflux of theophylline at the adult blood-brain barrier.
History
Publication title
Clinical and Experimental Pharmacology and PhysiologyVolume
25Issue
5Pagination
361-368ISSN
0305-1870Department/School
Tasmanian School of MedicinePublisher
Blackwell Publishing AsiaPlace of publication
54 University St, P O Box 378, Carlton, Australia, Victoria, 3053Repository Status
- Restricted