Drug Design, Development and Therapy (Sep 2023)
Escitalopram Personalized Dosing: A Population Pharmacokinetics Repository Method
Abstract
Xin Liu,1– 3 Gehang Ju,1– 3 Wenyu Yang,4 Lulu Chen,3,5,6 Nuo Xu,4 Qingfeng He,4 Xiao Zhu,4,* Dongsheng Ouyang1– 3,5,* 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institute of Clinical Pharmacology, Central South University, Changsha, People’s Republic of China; 3Hunan Key Laboratory for Bioanalysis of Complex Matrix Samples, Changsha Duxact Biotech Co., Ltd, Changsha, People’s Republic of China; 4Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Shanghai, People’s Republic of China; 5Changsha Duxact Biotech Co., Ltd, Changsha, People’s Republic of China; 6Department of Pharmacy, Affiliated Hospital of Xiangnan University, Chenzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dongsheng Ouyang, Changsha Duxact Biotech Co., Ltd, Lutian Road 28, Changsha, 410221, People’s Republic of China, Tel +86 0731-84805380, Email [email protected] Xiao Zhu, Department of Clinical Pharmacy and Pharmacy Administration, School of Pharmacy, Fudan University, Zhangheng Road 826, Shanghai, 201203, People’s Republic of China, Tel +862151980024, Email [email protected]: Escitalopram (SCIT) represents a first-line antidepressant and antianxiety medication. Pharmacokinetic studies of SCIT have demonstrated considerable interindividual variability, emphasizing the need for personalized dosing. Accordingly, we aimed to create a repository of parametric population pharmacokinetic (PPK) models of SCIT to facilitate model-informed precision dosing. In November 2022, we searched PubMed, Embase, and Web of Science for published PPK models and identified eight models. All the structural models reported in the literature were either one- or two-compartment models. In order to investigate the variances in model performance, the parameters of all PPK models were derived from the literature published. A representative virtual population, characterized by an age of 30, a body weight of 70 kg, and a BMI of 23 kg/m2, was generated for the purpose of replicating these models. To accomplish this, the rxode2 package in the R programming language was employed. Subsequently, we compared simulated concentration–time profiles and evaluated the impact of covariates on clearance. The most significant covariates were CYP2C19 phenotype, weight, and age, indicating that dosing regimens should be tailored accordingly. Additionally, among Chinese psychiatric patients, SCIT showed nearly double the exposure compared to other populations, specifically when considering the same CYP2C19 population restriction, which is a knowledge gap that needs further investigation. Furthermore, this repository of parametric PPK models for SCIT has a wide range of potential applications, like design miss or delay dose remedy strategies and external PPK model validation.Keywords: escitalopram, population pharmacokinetics, precision medicine, CYP2C19
