{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,11]],"date-time":"2026-07-11T14:29:07Z","timestamp":1783780147795,"version":"3.55.0"},"reference-count":27,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>To evaluate the adequacy of different dosing regimens of voriconazole for the prophylaxis of invasive candidiasis and aspergillosis in adult allogeneic stem cell transplant recipients by means of population pharmacokinetic (PK) modelling and simulation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Allogeneic stem cell transplant recipients receiving voriconazole were included in this observational study. A population PK model was developed. Three oral voriconazole-dosing regimens were simulated: 200, 300, and 400 mg twice daily. The pharmacodynamic target was defined as <jats:italic toggle=\"yes\">f<\/jats:italic>AUC<jats:sub>0\u201324<\/jats:sub>\/0.7. A probability of target attainment \u226590% was considered optimal. The cumulative fraction of response was defined as the fraction of patients achieving the pharmacodynamic target when a population of simulated patients is matched with a simulated population of different <jats:italic toggle=\"yes\">Candida<\/jats:italic> spp. and <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic> spp. The percentage of patients with trough plasma concentrations at steady state (C<jats:sub>trough<\/jats:sub>) within the reference range (1\u20135.5 mg\/L) was also calculated.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>A 2-compartment PK model was developed using data from 40 patients, which contributed 237 voriconazole plasma samples, including trough and maximum concentrations. Voriconazole 200, 300, and 400 mg twice daily achieved probability of target attainment \u226590% for minimal inhibitory concentration values \u22640.25, \u22640.38, and \u22640.50 mg\/L, respectively. The cumulative fraction of response for <jats:italic toggle=\"yes\">A. niger<\/jats:italic>, <jats:italic toggle=\"yes\">A. versicolor<\/jats:italic>, and <jats:italic toggle=\"yes\">A. flavus<\/jats:italic> increased &gt;10% when increasing voriconazole dose from 200 to 400 mg twice daily (from 72.5% to 89.5% for <jats:italic toggle=\"yes\">A. niger<\/jats:italic>; from 77.7% to 88.7% for <jats:italic toggle=\"yes\">A. versicolor<\/jats:italic>; and from 82.4% to 94.9% for <jats:italic toggle=\"yes\">A flavus<\/jats:italic>). The percentage of patients with C<jats:sub>trough<\/jats:sub> within the reference range increased 15% when voriconazole dose was increased from 200 to 300 mg twice daily.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>The PK simulations in this study suggest that transplant recipients on voriconazole prophylaxis against invasive candidiasis or aspergillosis are likely to achieve the target concentrations associated with the desired treatment outcomes if the maintenance dose is 200 mg twice daily. However, <jats:italic toggle=\"yes\">Aspergillus<\/jats:italic> spp. with high minimal inhibitory concentrations could require higher maintenance doses.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000657","type":"journal-article","created":{"date-parts":[[2019,5,27]],"date-time":"2019-05-27T09:03:35Z","timestamp":1558947815000},"page":"740-747","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacokinetic\/Pharmacodynamic Analysis of Voriconazole Against Candida spp. and Aspergillus spp. in Allogeneic Stem Cell Transplant Recipients"],"prefix":"10.1097","volume":"41","author":[{"given":"Alejandro","family":"Perez-Pitarch","sequence":"first","affiliation":[{"name":"Pharmacy Department, University Clinical Hospital of Valencia, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beatriz","family":"Guglieri-Lopez","sequence":"additional","affiliation":[{"name":"Pharmacy Department, Doctor Peset University Hospital, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rafael","family":"Ferriols-Lisart","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Clinical Hospital of Valencia, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ariadna","family":"P\u00e9rez","sequence":"additional","affiliation":[{"name":"Haematology Department, University Clinical Hospital of Valencia, Valencia, Spain. Dr. Pi\u00f1ana Is now with the Haematology Service, Hospital Universitario y Polit\u00e9cnico Louisiana Fe, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Ezquer-Gar\u00edn","sequence":"additional","affiliation":[{"name":"Institute for Health Research (INCLIVA), University Clinical Hospital of Valencia, Valencia, Spain; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan C.","family":"Hern\u00e1ndez-Boluda","sequence":"additional","affiliation":[{"name":"Haematology Department, University Clinical Hospital of Valencia, Valencia, Spain. Dr. Pi\u00f1ana Is now with the Haematology Service, Hospital Universitario y Polit\u00e9cnico Louisiana Fe, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose L.","family":"Pi\u00f1ana","sequence":"additional","affiliation":[{"name":"Haematology Department, University Clinical Hospital of Valencia, Valencia, Spain. Dr. Pi\u00f1ana Is now with the Haematology Service, Hospital Universitario y Polit\u00e9cnico Louisiana Fe, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Navarro","sequence":"additional","affiliation":[{"name":"Microbiology Service, Hospital Cl\u00ednico Universitario, Valencia, Spain."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Solano","sequence":"additional","affiliation":[{"name":"Haematology Department, University Clinical Hospital of Valencia, Valencia, Spain. Dr. Pi\u00f1ana Is now with the Haematology Service, Hospital Universitario y Polit\u00e9cnico Louisiana Fe, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuel","family":"Al\u00f3s-Almi\u00f1ana","sequence":"additional","affiliation":[{"name":"Pharmacy Department, University Clinical Hospital of Valencia, Valencia, Spain;"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-20230814","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1093\/jac\/dkp416","article-title":"Pharmacokinetics and safety of 14 days intravenous voriconazole in allogeneic haematopoietic stem cell transplant recipients","volume":"65","author":"Bruggemann","year":"2010","journal-title":"J Antimicrob Chemother."},{"key":"R2-20230814","doi-asserted-by":"crossref","first-page":"2305","DOI":"10.1128\/AAC.04838-14","article-title":"Variability of voriconazole plasma concentrations after allogeneic hematopoietic stem cell 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Pharmacokinet."},{"key":"R8-20230814","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 dosing","volume":"69","author":"Dolton","year":"2014","journal-title":"J Antimicrob Chemother."},{"key":"R9-20230814","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.jchromb.2008.02.009","article-title":"Determination of voriconazole in human plasma and saliva using high-performance liquid chromatography with fluorescence detection","volume":"865","author":"Michael","year":"2008","journal-title":"J Chromatogr B Anal Technol Biomed Life Sci."},{"key":"R13-20230814","article-title":"Mrgsolve: simulate from ODE-based models","author":"Baron","year":"2019"},{"key":"R14-20230814","doi-asserted-by":"crossref","first-page":"6782","DOI":"10.1128\/AAC.03641-14","article-title":"Impact of hypoalbuminemia on voriconazole pharmacokinetics 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Dis."},{"key":"R17-20230814","doi-asserted-by":"crossref","first-page":"381","DOI":"10.1093\/cid\/cis437","article-title":"Challenging recommended oral and intravenous voriconazole doses for improved efficacy and safety: population pharmacokinetics-based analysis of adult patients with invasive fungal infections","volume":"55","author":"Pascual","year":"2012","journal-title":"Clin Infect Dis."},{"key":"R18-20230814","doi-asserted-by":"crossref","first-page":"687","DOI":"10.1007\/s40262-019-00735-7","article-title":"Voriconazole: a review of population pharmacokinetic analyses","volume":"58","author":"Shi","year":"2019","journal-title":"Clin Pharmacokinet."},{"key":"R19-20230814","doi-asserted-by":"crossref","first-page":"2234","DOI":"10.1093\/jac\/dkw127","article-title":"Voriconazole pharmacokinetics following HSCT: results from the BMT CTN 0101 trial","volume":"71","author":"Hope","year":"2016","journal-title":"J Antimicrob 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