Pharmacokinetic Modeling of Non-Linear Brain Distribution of Fluvoxamine in the Rat

Introduction. A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine. Materials and methods. Rats with arterial and venous cannulas and a microdialysis probe in the frontal cortex received intravenous infusions of 1, 3.7 or 7.3 mg.kg j1 of fluvoxamine. Analysis. With increasing dose a disproportional increase in brain concentrations was observed. Th