{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T10:11:27Z","timestamp":1792145487571,"version":"4.4.0"},"reference-count":38,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2024,10,17]],"date-time":"2024-10-17T00:00:00Z","timestamp":1729123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010564","name":"Deutsche Zentrum f\u00fcr Lungenforschung (DZL)","doi-asserted-by":"publisher","award":["FKZ 82DZLJ73B2"],"award-info":[{"award-number":["FKZ 82DZLJ73B2"]}],"id":[{"id":"10.13039\/501100010564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background\/Objectives: Elexacaftor, tezacaftor, and ivacaftor (ETI) have significantly improved lung function in people with cystic fibrosis (pwCF). Despite exceptional improvements in most cases, treatment-related inter-subject variability and drug\u2013drug interactions that complicate modulator therapy have been reported. Methods: This retrospective analysis presents data on the serum concentration of ETI in our pwCF with full or reduced dosage from August 2021 to December 2023 via routine therapeutic drug monitoring (TDM). The data were compared with the maximum drug concentrations (Cmax) from the pharmaceutical company\u2019s summary of product characteristics. Results: A total of 786 blood samples from 155 pwCF (41% female, 59% male) were analyzed. The examinations were divided into four groups: full dose within the given tmax (38.5% of all measurements), full dose outside the tmax (29%), reduced dose within the tmax (19.2%), and reduced dose outside the tmax (13.2%). In pwCF receiving the full dose and blood taken within the tmax, 45.3% of serum concentrations of elexacaftor, 51.1% of serum concentrations of ivacaftor, and 8.9% of serum concentrations of tezacaftor were found to be above the Cmax, respectively. For those on reduced doses within the tmax, 24.5% had a serum concentration of elexacaftor, 23.2% had a serum concentration of ivacaftor, and 2.5% had a serum concentration of tezacaftor above the Cmax, respectively. Conclusions: Many pwCF under ETI therapy have Cmax values for elexacaftor and ivacaftor above the recommended range, even on reduced doses or before the tmax was reached. This highlights the value of a TDM program. Further pharmacokinetic studies are necessary.<\/jats:p>","DOI":"10.3390\/jpm14101065","type":"journal-article","created":{"date-parts":[[2024,10,18]],"date-time":"2024-10-18T05:03:49Z","timestamp":1729227829000},"page":"1065","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Therapeutic Drug Monitoring of Elexacaftor, Tezacaftor, and Ivacaftor in Adult People with Cystic Fibrosis"],"prefix":"10.3390","volume":"14","author":[{"given":"Susanne","family":"Naehrig","sequence":"first","affiliation":[{"name":"Cystic Fibrosis Center for Adults, Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Shad","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center for Adults, Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Breuling","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center for Adults, Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Goetschke","sequence":"additional","affiliation":[{"name":"Cystic Fibrosis Center for Adults, Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), 80336 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5110-346X","authenticated-orcid":false,"given":"Katharina","family":"Habler","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 813777 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Sieber","sequence":"additional","affiliation":[{"name":"STAT-UP Statistical Consulting & Data Science GmbH, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johanna","family":"Kastenberger","sequence":"additional","affiliation":[{"name":"STAT-UP Statistical Consulting & Data Science GmbH, 80333 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9849-9901","authenticated-orcid":false,"given":"Alexandra Katharina","family":"Kunzelmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3941-8944","authenticated-orcid":false,"given":"Olaf","family":"Sommerburg","sequence":"additional","affiliation":[{"name":"Division of Pediatric Pulmonology, Allergy and Cystic Fibrosis Center, Department of Pediatrics, University Hospital Heidelberg, Member of the German Center for Lung Research (DZL), 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4375-0923","authenticated-orcid":false,"given":"Uwe","family":"Liebchen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, LMU University Hospital, LMU Munich, 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9151-4829","authenticated-orcid":false,"given":"Juergen","family":"Behr","sequence":"additional","affiliation":[{"name":"Department of Medicine V, LMU University Hospital, LMU Munich, Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), 81377 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Vogeser","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 813777 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8831-0238","authenticated-orcid":false,"given":"Michael","family":"Paal","sequence":"additional","affiliation":[{"name":"Institute of Laboratory Medicine, LMU University Hospital, LMU Munich, 813777 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2195","DOI":"10.1016\/S0140-6736(20)32542-3","article-title":"Cystic fibrosis","volume":"397","author":"Shteinberg","year":"2021","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2519","DOI":"10.1016\/S0140-6736(16)00576-6","article-title":"Cystic fibrosis","volume":"388","author":"Elborn","year":"2016","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113195","DOI":"10.1016\/j.ejmech.2021.113195","article-title":"Updates on clinical development and future directions","volume":"213","author":"Bardin","year":"2021","journal-title":"Eur. 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