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Defining the therapeutic reference range and optimizing a high-dose discontinuation strategy for Paroxetine based on
Wanting Huang1, Xiaolin Li2, Shanqing Huang1
1The Affiliated Brain Hospital, School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, PR China; Key Laboratory of Neurogenetics and Channelopathies of Guangdong Province and the Ministry of Education of China, Guangzhou Medical University, Guangzhou, PR China.
Abstract:
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.
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