PERMEABILITY OF THE DEVELOPING AND MATURE BLOOD-BRAIN BARRIERS TO THEOPHYLLINE IN RATS

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 wer e reached within Ih following a single intraperitoneal (i.p.) injectio n, 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 significant ly higher than ratios in adult rats. Steady state ratios for theophyll ine were significantly higher than those for L-glucose in both neonata l 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 neo natal or adult rats. In contrast, steady state CSF:plasma and brain:pl asma ratios for L-glucose were increased by respiratory acidosis. 4. T he 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 neonate s, with a greater retention of protein-bound (non-exchangeable) theoph ylline in adult blood, and are unlikely to be due to p-glycoprotein-me diated efflux of theophylline at the adult blood-brain barrier.