{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T14:29:08Z","timestamp":1783780148467,"version":"3.55.0"},"reference-count":28,"publisher":"Public Library of Science (PLoS)","issue":"3","license":[{"start":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T00:00:00Z","timestamp":1743033600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Scientific Research Deanship at University of Hail- Saudi Arabia","award":["RG 23 149"],"award-info":[{"award-number":["RG 23 149"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:sec id=\"sec001\">\n<jats:title>Purpose<\/jats:title>\n<jats:p>The pharmacokinetics of voriconazole have been studied across various populations but data specific to the Pakistani cancer population has not yet been reported. The aim of present study was to explore and identify covariates that affect pharmacokinetics of intravenous voriconazole in Pakistani cancer population.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec002\">\n<jats:title>Methods<\/jats:title>\n<jats:p>The therapeutic drug monitoring data from January1<jats:sup>st<\/jats:sup>, 2023 to December 31<jats:sup>st<\/jats:sup>, 2023 of cancer patients receiving intravenous voriconazole for systemic fungal infections were taken from electronic medical record of the hospital. The data were used for the development of population pharmacokinetic model using NONMEM. Impact of various covariates such as age, weight, sex, liver function test, serum creatinine, creatinine clearance, type of cancer (primary diagnosis) and type of fungal infection were assessed through stepwise covariate modeling. Bootstrap analysis and goodness of fit plots were used to evaluate robustness and predictive performance of final model.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec003\">\n<jats:title>Results<\/jats:title>\n<jats:p>One compartment model best described the included data with first order elimination. The value of voriconazole clearance was 6.17\u2009L\/h with interindividual variability of 83.7% while volume of distribution was 55.9\u2009L. The clearance of voriconazole was significantly influenced by renal status of patients. Creatinine clearance and primary diagnosis were significant covariates affecting clearance of voriconazole in covariate analysis.<\/jats:p>\n<\/jats:sec>\n<jats:sec id=\"sec004\">\n<jats:title>Conclusion<\/jats:title>\n<jats:p>The findings suggest that this model can be used for dosage adjustment based on creatinine clearance and primary diagnosis as they impact significantly on voriconazole clearance in cancer patients. This approach is especially valuable in resource-limited settings like Pakistan, where individualized therapy can enhance the safety and efficacy of antifungal treatment, addressing the unique clinical and demographic challenges in vulnerable populations.<\/jats:p>\n<\/jats:sec>","DOI":"10.1371\/journal.pone.0318883","type":"journal-article","created":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T18:26:47Z","timestamp":1743100007000},"page":"e0318883","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Population pharmacokinetic analysis of intravenous voriconazole in cancer patients"],"prefix":"10.1371","volume":"20","author":[{"given":"Zunaira","family":"Akbar","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4854-1888","authenticated-orcid":true,"given":"Muhammad","family":"Usman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad","family":"Aamir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zikria","family":"Saleem","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Rehan","family":"Khan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulwahab","family":"Alamri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Salem","family":"Alharbi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal Eldin Mohamed","family":"Osman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"issue":"4","key":"pone.0318883.ref001","doi-asserted-by":"crossref","first-page":"e1-50","DOI":"10.1093\/cid\/civ1194","article-title":"Clinical practice guideline for the management of candidiasis: 2016 update by the infectious diseases society of America","volume":"62","author":"PG Pappas","year":"2016","journal-title":"Clin Infect Dis"},{"issue":"2","key":"pone.0318883.ref002","doi-asserted-by":"crossref","first-page":"227","DOI":"10.3390\/jcm8020227","article-title":"A personalized CYP2C19 phenotype-guided dosing regimen of voriconazole using a population pharmacokinetic analysis","volume":"8","author":"Y Kim","year":"2019","journal-title":"J Clin 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voriconazole: over a decade of use","volume":"30","author":"MT Levine","year":"2016","journal-title":"Clin Transplant"},{"issue":"8","key":"pone.0318883.ref012","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/BF03261928","article-title":"Fundamentals of population pharmacokinetic modelling: modelling and software","volume":"51","author":"TKL Kiang","year":"2012","journal-title":"Clin Pharmacokinet"},{"issue":"10","key":"pone.0318883.ref013","doi-asserted-by":"crossref","first-page":"4424","DOI":"10.1128\/AAC.00504-10","article-title":"Bioavailability and population pharmacokinetics of voriconazole in lung transplant recipients","volume":"54","author":"K Han","year":"2010","journal-title":"Antimicrob Agents Chemother"},{"issue":"6","key":"pone.0318883.ref014","doi-asserted-by":"crossref","first-page":"1633","DOI":"10.1093\/jac\/dku031","article-title":"Understanding variability with voriconazole using a population pharmacokinetic approach: implications for optimal 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Population pharmacokinetics in China: the dynamics of intravenous voriconazole in critically ill patients with pulmonary disease. 2015.","DOI":"10.1248\/bpb.b14-00768"},{"issue":"6","key":"pone.0318883.ref027","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.jiac.2019.01.015","article-title":"The effects of antifungal stewardship programs at a tertiary-care teaching hospital in Japan","volume":"25","author":"H Kawaguchi","year":"2019","journal-title":"J Infect Chemother"},{"issue":"8","key":"pone.0318883.ref028","doi-asserted-by":"crossref","first-page":"4718","DOI":"10.1128\/AAC.02808-13","article-title":"Population pharmacokinetic analysis of voriconazole and anidulafungin in adult patients with invasive aspergillosis","volume":"58","author":"P Liu","year":"2014","journal-title":"Antimicrob Agents Chemother"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318883","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,3,27]],"date-time":"2025-03-27T18:27:36Z","timestamp":1743100056000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0318883"}},"subtitle":[],"editor":[{"given":"Ali","family":"Amanati","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,3,27]]},"references-count":28,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0318883","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,27]]}}}