Population pharmacokinetic modeling: A step toward precision dosing

Abstract

Precision medicine is an approach to tailoring disease prevention and treatment based on individual patient characteristics, aiming to deliver the right treatment to the right patient at the right time. Precision dosing relies on clinical tools capable of integrating genotypic and phenotypic characteristics to inform individualized dosing strategies. Traditional Therapeutic Drug Monitoring (TDM) remains important for many drugs with a low therapeutic index, high pharmacokinetic variability, and a well-established relationship between drug concentration and effect. Moreover, population pharmacokinetic models have been widely implemented in clinical practice within the context of TDM, particularly to support model-informed precision dosing (MIPD). Population pharmacokinetic modeling and precision dosing strategies will be demonstrated in adult psychiatric patients treated with the antipsychotic Clozapine. Clozapine is a second-generation antipsychotic drug with superior efficacy in patients with treatment-resistant schizophrenia; however, it remains underused in clinical practice due to safety concerns and low therapeutic index. Multiple factors influence its pharmacokinetics, contributing to marked interand intra-individual variability in drug and metabolite levels, including demographic and pathological characteristics, smoking status, and co-therapy. According to the Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology, TDM is strongly recommended for Clozapine. Thus, optimizing therapy through precision dosing and MIPD is a promising strategy to enhance both the efficacy and safety of Clozapine treatment. Pharmacists, in collaboration with other healthcare professionals, play a significant role in individualizing dosing regimens, particularly within traditional TDM and more advanced precision dosing strategies.