CFTR Modulator Pharmacokinetics and Drug Monitoring from Pregnancy to Adulthood

Highly effective CFTR modulator therapy with elexacaftor/tezacaftor/ivacaftor has transformed the outlook for people with cystic fibrosis, but its use across the earliest and most dynamic stages of life remains poorly characterized. Children are not small adults: absorption, distribution, metabolism and elimination change continuously from the fetal period through infancy, childhood and adolescence as organ function matures, enzyme and transporter activity shifts, and body composition develops. These changes mean that drug exposure in a neonate, an infant or a growing child cannot be reliably predicted from adult dosing data. At the same time, more women with cystic fibrosis are now conceiving while on modulator therapy, raising urgent questions about transplacental transfer, drug concentrations in breast milk, and the exposure and safety of the fetus and breastfed infant.Evidence to guide clinicians across this continuum is limited and fragmented. Modulator concentrations vary widely between individuals even at identical doses, yet therapeutic drug monitoring (TDM) is not yet standard in pediatric care, and validated, minimally invasive sampling approaches suitable for children and infants are only beginning to emerge. Important uncertainties concern how modulator pharmacokinetics differ by age and developmental stage, how genetic variation shapes exposure and response, how to monitor drug levels safely in small children, and how treatment should be managed during pregnancy, lactation and the vulnerable transition from pediatric to adult services. Bringing together pharmacology, pediatrics, obstetrics and bedside prescribing in one place is essential to move toward individualized, evidence-based dosing.This Research Topic aims to advance the developmental pharmacology and therapeutic drug monitoring of CFTR modulators across pregnancy, lactation, childhood and the transition to adult care. We welcome clinical, translational, analytical and pharmacometric contributions that improve our understanding of drug exposure, safety and response in these populations. Themes include, but are not limited to:o Pharmacokinetics of CFTR modulators across neonatal, infant, childhood and adolescent developmento Transplacental transfer, breast-milk concentrations, and fetal and infant exposure during pregnancy and lactationo Therapeutic drug monitoring strategies and minimally invasive sampling (dried blood spot, nasal airway, sweat, saliva) in childreno Analytical method development and validation for modulator quantification in pediatric matriceso Pharmacogenomics and inter-individual variability in modulator exposure and responseo Airway versus systemic drug concentrations and their relationship to clinical outcomeso Drug-drug interactions, nutrition, and factors influencing modulator exposure in growing childreno Safety, tolerability, and long-term developmental outcomes of early-life modulator exposureo Modulator management during the transition from pediatric to adult careo Modelling, simulation and precision-dosing approaches for individualized pediatric therapyo Real-world evidence, registries and resource-sensitive monitoring strategiesWe welcome Original Research, Reviews, Mini-Reviews, Methods, Case Reports, Clinical Trials and Perspective articles that advance precision CFTR modulator therapy across the maternal-child-adolescent continuum. Topic editors: Matteo Mucci, Antonio Recchiuti, PIETRO RIPANI, Benedetta Fabrizzi Source: https://www.frontiersin.org/research-topics/85722/cftr-modulator-pharmacokinetics-and-drug-monitoring-from-pregnancy-to-adulthood