Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023 Sep 27:17:2955-2967.
doi: 10.2147/DDDT.S425654. eCollection 2023.

Escitalopram Personalized Dosing: A Population Pharmacokinetics Repository Method

Xin Liu  1   2   3 , Gehang Ju  1   2   3 , Wenyu Yang  4 , Lulu Chen  3   5   6 , Nuo Xu  4 , Qingfeng He  4 , Xiao Zhu #  4 , Dongsheng Ouyang #  1   2   3   5
Affiliations
Review

Escitalopram Personalized Dosing: A Population Pharmacokinetics Repository Method

Xin Liu et al. Drug Des Devel Ther. .

Abstract

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: CYP2C19; escitalopram; population pharmacokinetics; precision medicine.

PubMed Disclaimer

Conflict of interest statement

The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
PRISMA Diagram of population pharmacokinetic studies screen.
Figure 2
Figure 2
Escitalopram main pharmacokinetic parameters (Cmax and AUC0-τ) at steady state of missing phenotype, CYP2C19 poor metabolizers and CYP2C19 extensive metabolizers population. (A) The Cmax comparison between the missing phenotype population. (B) The Cmax comparison between the CYP2C19 extensive metabolizers population. (C) The Cmax comparison between the CYP2C19 poor metabolizers population. (D) The AUC0-τ comparison between the missing phenotype population. (E) The AUC0-τ comparison between the CYP2C19 extensive metabolizers population. (F) The AUC0-τ comparison between the CYP2C19 poor metabolizers population.
Figure 3
Figure 3
Investigated and Identified covariates of all the population pharmacokinetic models.
Figure 4
Figure 4
Forest plot of covariates effects on clearance of escitalopram.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. World Health Organization. World Mental Health Report: Transforming Mental Health for All. WHO; 2022.
    1. Malhi GS, Mann JJ. Depression. Lancet. 2018;392(10161):2299–2312. doi:10.1016/S0140-6736(18)31948-2 - DOI - PubMed
    1. Ho T, Pollock BG, Mulsant BH, et al. R- and S-citalopram concentrations have differential effects on neuropsychiatric scores in elders with dementia and agitation. Br J Clin Pharmacol. 2016;82(3):784–792. doi:10.1111/bcp.12997 - DOI - PMC - PubMed
    1. Jacquot C, David DJ, Gardier AM, Sánchez C. Escitalopram et Citalopram: le rôle inattendu de l’énantiomère R [Escitalopram and citalopram: the unexpected role of the R-enantiomer]. Encephale. 2007;33(2):179–187. doi:10.1016/s0013-7006(07)91548-1 - DOI - PubMed
    1. Pastoor D, Gobburu J. Clinical pharmacology review of escitalopram for the treatment of depression. Expert Opin Drug Metab Toxicol. 2014;10(1):121–128. doi:10.1517/17425255.2014.863873 - DOI - PubMed