Abstract
The purpose of this investigation is to quantitatively describe the pharmacoldnetics of theophylline (TP) and valproic acid (VPA) in guinea pig plasma, cerebrospinal fluid (CSF) andtear using a basic physiological model, and to characterize the correlation between tear and CSF concentrations on guinea pigs and patients. The time courses of TP and VPA concentrations in CSF and tear were similar to those of free concentrations in plasma and could be described by a basic physiological model in which the CSF and tear compartments are independently connected with the plasma compartments (free drugs) based on the apparent diffusion clearances. The CSF concentrations of TP and VPA at the steady state of both guinea pigs and patients could be predicted by the tear concentrations of them using the resulting pharmacokinetic parameters. These results indicated that the measurement of drug concentrations in tear which can be collected non-invasively is a very useful method for therapeutic drug monitoring of TP and VPA.
