{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:59:08Z","timestamp":1791593948168,"version":"4.3.4"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T00:00:00Z","timestamp":1746748800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Elexacaftor\/tezacaftor\/ivacaftor (ETI) significantly improves treatment outcomes for people with cystic fibrosis (pwCF) with at least one F508del allele. In 2023, the Food and Drug Administration approved ETI for children with CF aged 2\u20135\u2009years. However, real\u2010world pharmacokinetic\u2010pharmacodynamic data for ETI in pediatric and adult populations are still limited. This study aimed to characterize the population PK of ETI in children with CF (chCF) and evaluate current dosing recommendations. Population PK modeling was conducted using Monolix software on 150 ETI concentrations obtained from therapeutic drug (TDM) monitoring in 96 children with CF aged 2\u201318\u2009years, as part of the MODUL\u2010CF study. Area under the curve was derived from individual Bayesian pharmacokinetic estimates. A one\u2010compartment model with a lag time, first\u2010order absorption, and elimination best described the PK of elexacaftor\/ivacaftor, while the PK of tezacaftor followed a one\u2010compartment model with first\u2010order absorption and elimination. A large between\u2010subject variability was observed. The effect of body weight was significant on apparent clearance and volume of distribution parameters using allometric scaling. Children weighing 30\u201340\u2009kg who received the adult\u2010recommended dose showed higher drug exposure compared to adults with cystic fibrosis. This is the first study to describe the population pharmacokinetics of ETI in chCF aged 2\u201318\u2009years, revealing high between\u2010subject variability for all three drugs. In this context, TDM is likely essential for managing ETI exposure levels and guiding dosing adjustments. The appropriateness of current dosing recommendations for children under 12\u2009years old weighing 30\u201340\u2009kg remains to be clarified.<\/jats:p>","DOI":"10.1111\/cts.70245","type":"journal-article","created":{"date-parts":[[2025,5,9]],"date-time":"2025-05-09T09:59:08Z","timestamp":1746784748000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Elexacaftor\/Tezacaftor\/Ivacaftor Population Pharmacokinetics in Pediatric Patients With Cystic Fibrosis"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6818-221X","authenticated-orcid":false,"given":"Ngoc Hoa","family":"Truong","sequence":"first","affiliation":[{"name":"Pharmacologie et \u00c9valuations des Th\u00e9rapeutiques Chez L'Enfant et la Femme Enceinte Universit\u00e9 Paris Cit\u00e9, Inserm  Paris France"},{"name":"Service de Pharmacologie Clinique, H\u00f4pital Cochin, AP\u2010HP Universit\u00e9 Paris Cit\u00e9  Paris 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