Multimatrix Monitoring of CFTR Modulators Reflecting Systemic Exposure, Airway Targeting, and Sweat Compartment in People with Cystic Fibrosis

Multimatrix Monitoring of CFTR Modulators Reflecting Systemic Exposure, Airway Targeting, and Sweat Compartment in People with Cystic Fibrosis | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 13 June 2025 V1 Latest version Share on Multimatrix Monitoring of CFTR Modulators Reflecting Systemic Exposure, Airway Targeting, and Sweat Compartment in People with Cystic Fibrosis Authors : Matteo Mucci 0000-0003-0417-0720 [email protected] , Martina Colarelli , Pietro Ripani , Marta Di Nicola , Marianna Del Ciotto , Maria Di Sabatino , Francesca Collini , Mario Romano , and Antonio Recchiuti Authors Info & Affiliations https://doi.org/10.22541/au.174983623.39912131/v1 220 views 129 downloads Contents Abstract Supplementary Material Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Cystic fibrosis (CF) is a severe genetic disorder caused by mutations in the CFTR gene, leading to impaired chloride transport and multi-organ epithelial dysfunction. The advent of CFTR modulators, particularly the triple therapy elexacaftor/tezacaftor/ivacaftor (ETI), has revolutionized CF treatment. However, inter-individual variability in therapeutic response remains a challenge, often linked to pharmacokinetic (PK) differences. While plasma remains the standard for PK studies, its invasiveness limits its utility, especially in pediatric and outpatient settings. In this study, we advanced a multidimensional PK framework by combining plasma and dried blood spot (DBS) analysis with novel, non-invasive sampling from nasal swabs (NAS) and sweat. Building on validated LC-MS/MS protocols, we demonstrated that DBS offers a reliable surrogate for plasma in monitoring systemic drug exposure. Moreover, we introduced new methods for detecting ETI concentrations in NAS and sweat, enabling the assessment of local drug distribution in airway surfaces and sweat glands-tissues critical to CF pathology. This truly minimally invasive integrative approach supports a more personalized and mechanistically informed strategy for therapeutic drug monitoring in CF, potentially enhancing the prediction of clinical response to CFTR modulation. Supplementary Material File (mucci combined pdf.pdf) Download 1.69 MB Information & Authors Information Version history V1 Version 1 13 June 2025 Copyright This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License Keywords cftr modulators cystic fibrosis (cf) inflammation lc-ms/ms therapeutic drug monitoring Authors Affiliations Matteo Mucci 0000-0003-0417-0720 [email protected] Department of Medical, Oral, and Biotechnology Science (DSMOB), Center of Advanced Studies and Technology, G. d'Annunzio University of Chieti -Pescara View all articles by this author Martina Colarelli Department of Medical, Oral, and Biotechnology Science (DSMOB), Center of Advanced Studies and Technology, G. d'Annunzio University of Chieti -Pescara View all articles by this author Pietro Ripani Regional CF Center, San Liberatore Hospital -ASL Teramo View all articles by this author Marta Di Nicola Department of Medical, Oral, and Biotechnology Science (DSMOB), Center of Advanced Studies and Technology, G. d'Annunzio University of Chieti -Pescara View all articles by this author Marianna Del Ciotto Regional CF Center, San Liberatore Hospital -ASL Teramo View all articles by this author Maria Di Sabatino Regional CF Center, San Liberatore Hospital -ASL Teramo View all articles by this author Francesca Collini Regional CF Center, San Liberatore Hospital -ASL Teramo View all articles by this author Mario Romano Department of Medical, Oral, and Biotechnology Science (DSMOB), Center of Advanced Studies and Technology, G. d'Annunzio University of Chieti -Pescara View all articles by this author Antonio Recchiuti Department of Medical, Oral, and Biotechnology Science (DSMOB), Center of Advanced Studies and Technology, G. d'Annunzio University of Chieti -Pescara View all articles by this author Funding Information Fondazione per la Ricerca sulla Fibrosi Cistica FFC#13/2024 Antonio Recchiuti Metrics & Citations Metrics Article Usage 220 views 129 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Matteo Mucci, Martina Colarelli, Pietro Ripani, et al. Multimatrix Monitoring of CFTR Modulators Reflecting Systemic Exposure, Airway Targeting, and Sweat Compartment in People with Cystic Fibrosis. Authorea . 13 June 2025. DOI: https://doi.org/10.22541/au.174983623.39912131/v1 If you have the appropriate software installed, you can download article citation data to the citation manager of your choice. Simply select your manager software from the list below and click Download. For more information or tips please see 'Downloading to a citation manager' in the Help menu . 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