{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T04:24:15Z","timestamp":1774585455853,"version":"3.50.1"},"reference-count":27,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Eastern Switzerland Foundation for Clinical Cancer Research"},{"name":"Roche Pharma AG Basel (Switzerland)"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Basic Clin Pharma Tox"],"published-print":{"date-parts":[[2017,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Erlotinib is metabolized by cytochrome p450 (<jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>) 3A and <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A. This study assessed <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>3A4 (midazolam) and <jats:styled-content style=\"fixed-case\">CYP<\/jats:styled-content>1A2 (caffeine) phenotyping in plasma and dried blood spots (<jats:styled-content style=\"fixed-case\">DBS<\/jats:styled-content>) for predicting the pharmacokinetics and toxicity of erlotinib in 36 patients with advanced <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>. On day 1, erlotinib 150\u00a0mg <jats:styled-content style=\"fixed-case\">OD<\/jats:styled-content> was initiated, and the two oral probe drugs midazolam (2\u00a0mg) and caffeine (100\u00a0mg) were added on day 1. Plasma and <jats:styled-content style=\"fixed-case\">DBS<\/jats:styled-content> were collected for erlotinib, <jats:styled-content style=\"fixed-case\">OSI<\/jats:styled-content>\u2010420 and probe drugs for up to 6\u00a0hr on day 1 and 2\u2010weekly up to week 10. Probe drugs, erlotinib and <jats:styled-content style=\"fixed-case\">OSI<\/jats:styled-content>\u2010420 were analysed using <jats:styled-content style=\"fixed-case\">LC<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>\u2010<jats:styled-content style=\"fixed-case\">MS<\/jats:styled-content>, and <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> data were processed using population modelling. A high correlation was found between plasma and <jats:styled-content style=\"fixed-case\">DBS<\/jats:styled-content> concentrations for erlotinib (<jats:italic>R<\/jats:italic><jats:sup>2\u00a0<\/jats:sup>=\u00a00.960, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001), <jats:styled-content style=\"fixed-case\">OSI<\/jats:styled-content>\u2010420 (<jats:italic>R<\/jats:italic><jats:sup>2\u00a0<\/jats:sup>=\u00a00.971, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001), midazolam (<jats:italic>R<\/jats:italic><jats:sup>2\u00a0<\/jats:sup>=\u00a00.995, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001) and caffeine (<jats:italic>R<\/jats:italic><jats:sup>2\u00a0<\/jats:sup>=\u00a00.968, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.0001). Apparent oral caffeine clearance was significantly correlated with erlotinib clearance (<jats:italic>R<\/jats:italic><jats:sup>2\u00a0<\/jats:sup>=\u00a00.33, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.048), while midazolam clearance was not (<jats:italic>R<\/jats:italic><jats:sup>2\u00a0<\/jats:sup>=\u00a0\u22120.09, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.596). Erlotinib clearance was lower in patients experiencing grade 2 or 3 rash as compared to patients experiencing grade 0 or 1 rash (3.15 <jats:italic>versus<\/jats:italic> 3.93\u00a0L\/hr, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.086 for Student's <jats:italic>t<\/jats:italic>\u2010test). The results suggest that probe drug phenotyping is unlikely to substitute therapeutic drug monitoring of erlotinib in patients with advanced <jats:styled-content style=\"fixed-case\">NSCLC<\/jats:styled-content>, but erlotinib <jats:styled-content style=\"fixed-case\">PK<\/jats:styled-content> sampling from <jats:styled-content style=\"fixed-case\">DBS<\/jats:styled-content> may replace more invasive venous sampling and facilitate <jats:styled-content style=\"fixed-case\">TDM<\/jats:styled-content> in patients with cancer.<\/jats:p>","DOI":"10.1111\/bcpt.12801","type":"journal-article","created":{"date-parts":[[2017,4,26]],"date-time":"2017-04-26T15:37:12Z","timestamp":1493221032000},"page":"309-315","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Role of Cytochrome P450 3A4 and 1A2 Phenotyping in Patients with Advanced Non\u2010small\u2010Cell Lung Cancer Receiving Erlotinib Treatment"],"prefix":"10.1111","volume":"121","author":[{"given":"Zinnia P.","family":"Parra\u2010Guillen","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy and Biochemistry Institute of Pharmacy Freie Universitaet Berlin Berlin Germany"},{"name":"Department of Pharmacy and Pharmaceutical Technology Universidad de Navarra Navarra Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter B.","family":"Berger","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology Department of Biomedicine University Hospital Basel University of Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"Haschke","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology Department of Biomedicine University Hospital Basel University of Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimiliano","family":"Donzelli","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology Department of Biomedicine University Hospital Basel University of Basel Basel Switzerland"},{"name":"Roche Pharma AG Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daria","family":"Winogradova","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; Toxicology Department of Biomedicine University Hospital Basel University of Basel Basel Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bogumila","family":"Pfister","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Cantonal Hospital St. Gallen St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin","family":"Fr\u00fch","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Cantonal Hospital St. Gallen St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silke","family":"Gillessen","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology and Hematology Cantonal Hospital St. Gallen St. Gallen Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephan","family":"Kr\u00e4henb\u00fchl","sequence":"additional","affiliation":[{"name":"Division of Clinical Pharmacology &amp; 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