{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T04:00:43Z","timestamp":1790913643944,"version":"4.1.0"},"reference-count":29,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":17,"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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Voriconazole (VRCZ) is a triazole antifungal agent with a broad antifungal spectrum. It is metabolized by hepatic cytochrome P450 (CYP) isozyme CYP2C19, whose genetic polymorphism causes significant variability in drug efficacy and safety. Poor metabolizer alleles of\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    are more common in Asian populations, increasing the risk of supratherapeutic VRCZ levels. We have developed a novel nomogram based on\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genetic polymorphisms. This study aimed to evaluate whether\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotype\u2010guided VRCZ therapy reduces toxicity in Japanese patients. This retrospective study included 64 patients (genotype\u2010guided group,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200926; comparison group,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200938). The primary outcome was defined as the composite incidence of adverse events commonly observed with VRCZ, represented by the combined occurrence of grade \u2265\u20092 hepatotoxicity and visual symptoms. Secondary outcomes included the proportion of patients maintaining VRCZ trough concentrations within the therapeutic range (1\u20134\u2009\u03bcg\/mL) and the treatment response at 28\u2009days. The composite incidence of adverse events was significantly lower in the genotype\u2010guided group than in the comparison group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.003). VRCZ discontinuation due to adverse events occurred in nine patients (23.7%) in the comparison group and one (3.8%) in the genotype\u2010guided group (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.039). More patients in the genotype\u2010guided group were achieved through concentrations within the therapeutic range at the initial sampling point. However, treatment response rates did not differ significantly between the groups. VRCZ administration based on\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotyping improved therapeutic trough levels management and reduced adverse effects while maintaining therapeutic efficacy. These findings highlight the importance of\n                    <jats:italic>CYP2C19<\/jats:italic>\n                    genotyping for VRCZ treatment in Japanese patients.\n                  <\/jats:p>","DOI":"10.1111\/cts.70317","type":"journal-article","created":{"date-parts":[[2025,8,19]],"date-time":"2025-08-19T01:39:26Z","timestamp":1755567566000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>\n                      <i>CYP2C19<\/i>\n                    <\/scp>\n                    \u2010Guided Voriconazole Therapy: A Precision Medicine Approach to Mitigate Adverse Effects in Japanese Patients"],"prefix":"10.1111","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0803-8823","authenticated-orcid":false,"given":"Yoshiki","family":"Katada","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8344-2469","authenticated-orcid":false,"given":"Daiki","family":"Hira","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1963-2510","authenticated-orcid":false,"given":"Keisuke","family":"Umemura","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3003-3238","authenticated-orcid":false,"given":"Yurie","family":"Katsube","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Ishimura","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Kojima","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machiko","family":"Hirai","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moto","family":"Kajiwara","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuhiro","family":"Sugimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroki","family":"Endo","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junru","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saki","family":"Ohta","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kinuka","family":"Kotani","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakiko","family":"Hatazoe","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9474-5107","authenticated-orcid":false,"given":"Masahiro","family":"Tsuda","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"},{"name":"Graduate School of Pharmaceutical Sciences Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1285-122X","authenticated-orcid":false,"given":"Shunsaku","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Therapeutics Kyoto University Hospital  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8934-0375","authenticated-orcid":false,"given":"Koh","family":"Shinohara","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Clinical Laboratory Medicine Graduate School of Medicine, Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1306-3652","authenticated-orcid":false,"given":"Yasuhiro","family":"Tsuchido","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Clinical Laboratory Medicine Graduate School of Medicine, Kyoto University  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8886-6145","authenticated-orcid":false,"given":"Miki","family":"Nagao","sequence":"additional","affiliation":[{"name":"Department of Infection Control and Prevention Kyoto University Hospital  Kyoto Japan"},{"name":"Department of Clinical Laboratory Medicine Graduate School of Medicine, Kyoto University  Kyoto 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Inc \u201cInterview Form of Voriconazole (Vfend) 50mg\/200mg.\u201dRevised in June 2024. 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