ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drug Metabolism and Transport
This article is part of the Research TopicAdvancements and Strategies in Predicting and Managing Clinical Drug-Drug InteractionsView all 8 articles
Enhanced CYP2C19-Mediated Drug-Drug Interaction Risk with Escitalopram in Geriatric Populations
Provisionally accepted
SeonYoung Byoun1
Dong-gyu Heo2Minsoo Lee1
Ryunghwa Lee1Yuanyuan Li1
Ju-Yeun Lee1Eunjin Hong2*
Wooin Lee1*- 1Seoul National University, Seoul, Republic of Korea
- 2Dongguk University College of Pharmacy, Goyang-si, Republic of Korea
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Escitalopram (S-CIT) is commonly prescribed for depression and anxiety in older patients. Previous research has reported that the effect of CYP2C19 polymorphism on S-CIT pharmacokinetics is more pronounced in older adults than in young adults. The current study investigated whether older adults taking S-CIT face a greater risk for CYP2C19-mediated drug-drug interaction (DDI) than young adults. Using a physiologically-based pharmacokinetic (PBPK) model, we quantitatively compared the risk of CYP2C19-mediated DDIs in older adults taking S-CIT with any of four CYP2C19 inhibitors (omeprazole, esomeprazole, fluconazole, and fluoxetine). These CYP2C19 inhibitors were selected based on their prevalence of co-administration with S-CIT, as determined by a retrospective analysis of the 2019 Korean National Health Insurance Service senior cohort database. Our PBPK modeling-based simulations predicted that the extent of DDI incurred by S-CIT would be greater in older adults than in young adults and vary significantly by CYP2C19 phenotypes (extensive, intermediate, and poor metabolizers). Based on the prediction results, we propose CYP2C19 phenotype-guided S-CIT dosing strategies for older adults. Implementing the proposed dosing recommendation may reduce the incidence of potentially inappropriate use of medication and adverse events in older adults prescribed S-CIT.
Keywords: escitalopram, CYP2C19, Geriatric population, drug-drug interactions, PBPK modeling
Received: 23 Sep 2025; Accepted: 02 Dec 2025.
Copyright: © 2025 Byoun, Heo, Lee, Lee, Li, Lee, Hong and Lee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Eunjin Hong
Wooin Lee
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