Observed and predicted distribution of acetaminophen in human brain. a) The human physiologically-based pharmacokinetic model which equals the rat physiologically-based pharmacokinetic model, but includes human instead of rat physiological parameters. (For the denotations in the model see Figure 4b). b) Acetaminophen concentrations in human plasma and brain. Data points represent observed data in human for plasma (black diamonds) and lumbar CSF (orange circles) by Bannwarth et al.. Lines represent predictions of human plasma concentrations (black line), human lumbar CSF concentrations (orange line, and human brain ECF concentrations (blue line) by the “humanized” preclinical physiologically-based PK model .