Distributed model for drug delivery to CSF and brain tissue.

Measurements of drug concentration in cerebrospinal fluid (CSF) provide the most accessible index of drug delivery to the brain. Our perception of the blood-brain barrier has been largely shaped by these measurements. A crucial question for the interpretation of these data is the nature of the relationships between drug concentration in CSF and the drug concentration profile in brain tissue. A distributed model for the delivery of drugs via plasma to brain tissue and CSF is presented, and the relationships between capillary exchange, tissue diffusion, and CSF turnover rate are explored. The effects of blood-brain barrier disruption on tissue and CSF concentrations are also simulated.