Defining the therapeutic reference range and optimizing a high-dose discontinuation strategy for Paroxetine based on TDM and population pharmacokinetics.

This study aimed to determine a clinically applicable therapeutic reference range for paroxetine across commonly prescribed doses. Based on therapeutic drug monitoring (TDM) data and population pharmacokinetics (PPK), we further developed a tapering strategy optimized for high-dose discontinuation. A one-compartment PPK model was established using TDM data from 360 hospitalized psychiatric patients. Daily dose and sex significantly influenced apparent clearance (CL/F), while formulation affected apparent volume of distribution (V/F). Simulations identified an effective serum concentration range of 15-125 ng/mL for males and 30-210 ng/mL for females. Given the higher concentrations associated with high doses, a more gradual tapering strategy is recommended. This study provides a practical therapeutic reference range and a discontinuation strategy specifically tailored for high-dose regimens.