Voriconazole Adjustment for Liver Dysfunction (VALID): From Population Pharmacokinetic Model to the Real-World

Voriconazole Adjustment for Liver Dysfunction (VALID): From Population Pharmacokinetic Model to the Real-World | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Voriconazole Adjustment for Liver Dysfunction (VALID): From Population Pharmacokinetic Model to the Real-World Huaiyuan Liu, Yichang Zhao, Jiakai Li, Zhihua Sun, Bikui Zhang, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5720035/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Objective Liver dysfunction affects drug metabolism, including voriconazole, used for treating fungal infections. This study evaluated the effectiveness and safety of a voriconazole dosing regimen adjusted for liver dysfunction (VALID) compared to standard dosing. Methods The study included liver dysfunction patients hospitalized between January 2020 and December 2023. Patients were divided into the VALID group and a control group. Data on demographics, medication, liver and kidney function, and adverse events were collected. Propensity score matching was used to balance the groups. Voriconazole levels were measured using liquid chromatography. Results The study analyzed 182 patients with 375 voriconazole measurements—39 in the VALID group and 143 in the control group. After matching, both groups were similar in baseline characteristics. The VALID group had a significantly higher target trough concentration achievement (89.7% vs. 48.7%, P < 0.0001) and lower initial voriconazole levels (2.46 mg/L vs. 4.13 mg/L, P = 0.0004). The VALID group also had fewer adverse events (15.4% vs. 38.5%, P = 0.02159). Efficacy between the two groups was similar (P = 0.9132). Factors like CYP2C19 phenotype and liver function influenced voriconazole levels. Conclusion The VALID regimen improved target trough levels and reduced adverse events compared to standard dosing. These findings support individualized dosing for better voriconazole therapy in liver dysfunction patients. Further research is needed to confirm these results in larger studies. Voriconazole Liver Dysfunction Dosing Regimen Total Bilirubin Therapeutic Drug Monitoring Full Text Additional Declarations No competing interests reported. Table 1 to 5 are available in the Supplementary Files section. Supplementary Files Table1.docx Table2.docx Table3.docx Table4.docx Table5.docx SupplementaryTable1.docx SupplementaryTable2.docx SupplementaryFigure1.png SupplementalryFigure1legend.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5720035","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":396259095,"identity":"00f4cb9e-01a9-4ae0-8dad-6344ec3d8e9d","order_by":0,"name":"Huaiyuan Liu","email":"","orcid":"","institution":"the Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Huaiyuan","middleName":"","lastName":"Liu","suffix":""},{"id":396259096,"identity":"54cfa4dc-be64-4991-9371-fd9dfa77f47d","order_by":1,"name":"Yichang Zhao","email":"","orcid":"","institution":"the Second Xiangya Hospital of Central 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Real-World","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Voriconazole, Liver Dysfunction, Dosing Regimen, Total Bilirubin, Therapeutic Drug Monitoring","lastPublishedDoi":"10.21203/rs.3.rs-5720035/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5720035/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eObjective\u003c/h2\u003e \u003cp\u003eLiver dysfunction affects drug metabolism, including voriconazole, used for treating fungal infections. This study evaluated the effectiveness and safety of a voriconazole dosing regimen adjusted for liver dysfunction (VALID) compared to standard dosing.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThe study included liver dysfunction patients hospitalized between January 2020 and December 2023. Patients were divided into the VALID group and a control group. Data on demographics, medication, liver and kidney function, and adverse events were collected. Propensity score matching was used to balance the groups. Voriconazole levels were measured using liquid chromatography.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study analyzed 182 patients with 375 voriconazole measurements\u0026mdash;39 in the VALID group and 143 in the control group. After matching, both groups were similar in baseline characteristics. The VALID group had a significantly higher target trough concentration achievement (89.7% vs. 48.7%, P\u0026thinsp;\u0026lt;\u0026thinsp;0.0001) and lower initial voriconazole levels (2.46 mg/L vs. 4.13 mg/L, P\u0026thinsp;=\u0026thinsp;0.0004). The VALID group also had fewer adverse events (15.4% vs. 38.5%, P\u0026thinsp;=\u0026thinsp;0.02159). Efficacy between the two groups was similar (P\u0026thinsp;=\u0026thinsp;0.9132). Factors like CYP2C19 phenotype and liver function influenced voriconazole levels.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThe VALID regimen improved target trough levels and reduced adverse events compared to standard dosing. These findings support individualized dosing for better voriconazole therapy in liver dysfunction patients. Further research is needed to confirm these results in larger studies.\u003c/p\u003e","manuscriptTitle":"Voriconazole Adjustment for Liver Dysfunction (VALID): From Population Pharmacokinetic Model to the Real-World","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-01-01 16:41:58","doi":"10.21203/rs.3.rs-5720035/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"e475cd46-0923-4a17-ba00-8110724560ae","owner":[],"postedDate":"January 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-02-01T06:08:28+00:00","versionOfRecord":[],"versionCreatedAt":"2025-01-01 16:41:58","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5720035","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5720035","identity":"rs-5720035","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}