{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T17:41:43Z","timestamp":1792086103839,"version":"4.4.0"},"reference-count":49,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,7,15]],"date-time":"2024-07-15T00:00:00Z","timestamp":1721001600000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Voriconazole is the cornerstone of the treatment and prevention of fungal infections. While there is a good correlation between\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype and voriconazole exposure during prophylactic treatment, no correlation was found in patients with invasive aspergillosis. Proinflammatory cytokines result in inhibition of CYP2C19 enzyme activity (and may result in phenoconversion). Here we investigated the relationship between inflammation,\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype\u2010predicted\u2010phenotype, and CYP2C19 activity in patients receiving voriconazole. Data were obtained from two prospective studies investigating voriconazole treatment (NCT02074462 and NCT00893555). Dose\u2010corrected voriconazole plasma concentration and C\u2010reactive protein (CRP) were used as proxies for CYP2C19 activity and inflammation, respectively. After data extraction and synthesis, data from 39 patients with paired voriconazole and CRP measurements were available. The distribution of\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype\u2010predicted metabolizer phenotypes was 31% intermediate (IM), 41% normal (NM), and 28% rapid metabolizer (RM). During inflammation, dose\u2010corrected voriconazole levels were increased by 245%, 278%, and 486% for CYP2C19 NMs IMs and RMs, respectively. Patients with moderate or high CRP levels (&gt;50\u2009mg\/L) were phenoconverted to a lower metabolizer phenotype irrespective of their\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype. In a subgroup analysis of eight patients with longitudinal data available with and without inflammation, the pattern of the dose\u2010corrected voriconazole and CRP measurements were similar, with CYP2C19 activity following decreasing or increasing CRP levels. In conclusion, voriconazole plasma concentrations increase during inflammation due to downregulation of CYP2C19 activity. While this effect appears largest for CYP2C19 RMs, no clinically relevant differences were observed between the\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotypes.\n                  <\/jats:p>","DOI":"10.1111\/cts.13887","type":"journal-article","created":{"date-parts":[[2024,7,16]],"date-time":"2024-07-16T02:20:19Z","timestamp":1721096419000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Inflammation altered correlation between\n                    <i>CYP2C19<\/i>\n                    genotype and\n                    <scp>CYP2C19<\/scp>\n                    activity in patients receiving voriconazole"],"prefix":"10.1111","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8124-5293","authenticated-orcid":false,"given":"Sylvia D.","family":"Klomp","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy &amp; Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-4451-4216","authenticated-orcid":false,"given":"Anette","family":"Veringa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen  Groningen The Netherlands"},{"name":"Apotheek, OLVG  Amsterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-0288","authenticated-orcid":false,"given":"Jan\u2010Willem C.","family":"Alffenaar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy and Pharmacology University Medical Center Groningen  Groningen The Netherlands"},{"name":"Faculty of Medicine and Health Sydney School of Pharmacy  Sydney New South Wales Australia"},{"name":"The University of Sydney Institute for Infectious Diseases  Sydney New South Wales Australia"},{"name":"Westmead Hospital  Sydney New South Wales Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5009-6499","authenticated-orcid":false,"given":"Mark G. J.","family":"de Boer","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0985-4649","authenticated-orcid":false,"given":"Lambert F. R.","family":"Span","sequence":"additional","affiliation":[{"name":"Department of Hematology University Medical Center Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7085-1383","authenticated-orcid":false,"given":"Henk\u2010Jan","family":"Guchelaar","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy &amp; Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3965-5552","authenticated-orcid":false,"given":"Jesse J.","family":"Swen","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy &amp; Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,7,15]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciy859"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s15010-013-0432-0"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/FTD.0b013e31817b1a95"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/0091270008327537"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jiac.2019.05.032"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.583"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-01004-7"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.18.48"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1641"},{"issue":"3","key":"e_1_2_9_11_1","first-page":"571","article-title":"Evaluation of CYP2C19 genotype\u2010guided voriconazole prophylaxis after allogeneic hematopoietic","volume":"107","author":"Patel JN","year":"2020","journal-title":"Cell Transplant"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2023.106711"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/jcm9092890"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.114.061093"},{"issue":"8","key":"e_1_2_9_15_1","first-page":"1415","article-title":"Effects of Interleukin\u20106 (IL\u20106) and an anti\u2010IL\u20106 monoclonal antibody on drug\u2010metabolizing enzymes in human hepatocyte","volume":"39","author":"Dickmann LJ","year":"2011","journal-title":"Culture"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2005-2213"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.02-0195fje"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2014.09.004"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2146"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12677"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248-019-0309-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3390\/genes11121509"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.733935"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02830-15"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.14661"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12422"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkw349"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jchromb.2009.11.017"},{"key":"e_1_2_9_29_1","unstructured":"American Board of Internal Medicine.American Board of Internal Medicine (ABIM).2023. 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