Theophylline blood-brain barrier transfer kinetics in dogs

A simple diffusion-based pharmacokinetic model is proposed relating blood-brain barrier transfer kinetics of theophylline to the difference in the free concentrations of the drug in serum and cerebrospinal fluid (CSF). The model predicts that the CSF drug level is proportional to the serum drug level convoluted by exp(-kt), where k is the blood-brain barrier diffusion rate constant. An excellent agreement was found by nonlinear regression analysis between serum and CSF theophylline data in eight dogs and the proposed model for the blood-brain barrier transfer kinetics of theophylline. The ratio of the free fractions of theophylline in serum and CSF predicted from the model also agrees with the value determined experimentally.