{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T04:27:57Z","timestamp":1786681677287,"version":"build-2736575974"},"reference-count":26,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100017659","name":"Uniscientia Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013363","name":"Lunge Z\u00fcrich","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013363","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["320030_173168"],"award-info":[{"award-number":["320030_173168"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["PCEGP3_181300"],"award-info":[{"award-number":["PCEGP3_181300"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Pharma and Therapeutics"],"abstract":"<jats:p>\n                    Accurate assessment of systemic drug exposure in humans remains challenging, as conventional approaches rely on intermittent blood sampling and laboratory\u2010based assays that are invasive and provide limited temporal resolution. Exhaled breath contains volatile and semi\u2010volatile compounds arising from drug metabolism and downstream biological processes, suggesting that it may serve as a non\u2010invasive matrix for integrated pharmacokinetic sensing. We conducted a prospective observational study using exhaled breath metabolomics based on secondary electrospray ionization high\u2010resolution mass spectrometry (SESI\u2010HRMS) to estimate systemic drug exposure from a breath\u2010sampling session. A total of 117 adults provided 127 paired breath\u2013serum measurements under routine outpatient conditions. Model performance was evaluated using repeated k\u2010fold cross\u2010validation and quantified using concordance correlation coefficients. Breath\u2010derived estimates of valproic acid, levetiracetam, lamotrigine, and lacosamide showed moderate concordance with measured serum concentrations, with concordance correlation coefficients ranging from 0.733 to 0.895 across medications. The lacosamide findings should be considered preliminary because of the limited subgroup size (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200916). The observed concordance supports proof\u2010of\u2010concept exposure estimation but does not establish clinical interchangeability with serum\u2010based therapeutic drug monitoring. The previously defined 11\u2010feature VPA breath signature retained predictive utility in a separate adult cohort, supporting its cross\u2010cohort transferability within the present analytical framework. These findings support the feasibility of exhaled breath analysis for non\u2010invasive estimation of systemic drug exposure across pharmacologically distinct medications. Breath analysis should currently be considered complementary to serum\u2010based monitoring, and external multicenter and longitudinal validation is required before clinical implementation.\n                  <\/jats:p>","DOI":"10.1002\/cpt.70437","type":"journal-article","created":{"date-parts":[[2026,8,8]],"date-time":"2026-08-08T03:24:20Z","timestamp":1786159460000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Non\u2010Invasive Estimation of Systemic Drug Exposure Using Exhaled Breath Metabolomics in Humans: A Translational Proof\u2010of\u2010Concept Study"],"prefix":"10.1002","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-5238-372X","authenticated-orcid":false,"given":"Kai","family":"Fricke","sequence":"first","affiliation":[{"name":"Department of Pulmonology University Hospital Zurich  Zurich Switzerland"},{"name":"Faculty of Medicine University of Zurich  Zurich 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Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathrin","family":"M\u00fcsch","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital Zurich  Zurich Switzerland"},{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1758-4586","authenticated-orcid":false,"given":"Noriane A.","family":"Sievi","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital Zurich  Zurich Switzerland"},{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9571-5736","authenticated-orcid":false,"given":"Marco","family":"Di Donato","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Department of Neurology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4087-2121","authenticated-orcid":false,"given":"Anton","family":"Schmick","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"},{"name":"Department of Neurology University Hospital Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3390-5741","authenticated-orcid":false,"given":"Jonas","family":"Herth","sequence":"additional","affiliation":[{"name":"Department of Pulmonology University Hospital Zurich  Zurich Switzerland"},{"name":"Faculty of Medicine University of Zurich  Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5250-5022","authenticated-orcid":false,"given":"Silvia","family":"Ulrich","sequence":"additional","affiliation":[{"name":"Department of 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