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PERMEABILITY OF THE DEVELOPING AND MATURE BLOOD‐BRAIN BARRIERS TO THEOPHYLLINE IN RATS
Author(s) -
Habgood MD,
Knott GW,
Dziegielewska KM,
Saunders NR
Publication year - 1998
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1111/j.1440-1681.1998.tb02364.x
Subject(s) - theophylline , medicine , endocrinology , cerebrospinal fluid , steady state (chemistry) , chemistry , respiratory system , blood plasma
SUMMARY 1. 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 intraperitoneal (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.