{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:47:52Z","timestamp":1791276472910,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2015,4,1]],"date-time":"2015-04-01T00:00:00Z","timestamp":1427846400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Voriconazole (VRC) plasma trough concentrations (\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            ) are highly variable, and this could affect treatment efficacy and safety in patients undergoing allogeneic hematopoietic stem cell transplantation (AHSCT). We aimed to describe the intra- and interindividual variation of VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            throughout the course of VRC therapy and to identify the determinants of this variation. Clinical data, medications, and VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            (\n            <jats:italic>n<\/jats:italic>\n            = 308) of 33 AHSCT patients were retrospectively collected. Cytochrome P450 (CYP450) genotypes of CYP2C19, CYP3A4, and CYP3A5 patients were retrospectively determined before allografting, and a combined genetic score was calculated for each patient. The higher the genetic score, the faster the metabolism of the patient. The VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            inter- and intraindividual coefficients of variation were 84% and 68%, respectively. The VRC dose (\n            <jats:italic>D<\/jats:italic>\n            ) was correlated to VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            (\n            <jats:italic>r<\/jats:italic>\n            = 0.412,\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001) only for oral administration. The administration route and the genetic score significantly affected the initial VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            . Considering oral therapy, patients with a genetic score of &lt;2 had higher initial VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            \/\n            <jats:italic>D<\/jats:italic>\n            than patients with a genetic score of &gt;2 (\n            <jats:italic>P<\/jats:italic>\n            = 0.009). Subsequent VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            remained influenced by the genetic score (\n            <jats:italic>P<\/jats:italic>\n            = 0.004) but were also affected by pump proton inhibitor comedication (\n            <jats:italic>P<\/jats:italic>\n            &lt; 0.0001). The high variability of VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            in AHSCT patients is partially explained by the route of administration, treatment with pump proton inhibitors, and the combined genetic score. This study suggests the interest in combined genetic score determination to individualize\n            <jats:italic>a priori<\/jats:italic>\n            the VRC dose and underlines the need for longitudinal therapeutic drug monitoring to adapt subsequent doses to maintain the VRC\n            <jats:italic>C<\/jats:italic>\n            <jats:sub>min<\/jats:sub>\n            within the therapeutic range.\n          <\/jats:p>","DOI":"10.1128\/aac.04838-14","type":"journal-article","created":{"date-parts":[[2015,2,3]],"date-time":"2015-02-03T06:04:54Z","timestamp":1422943494000},"page":"2305-2314","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":64,"title":["Variability of Voriconazole Plasma Concentrations after Allogeneic Hematopoietic Stem Cell Transplantation: Impact of Cytochrome P450 Polymorphisms and Comedications on Initial and Subsequent Trough Levels"],"prefix":"10.1128","volume":"59","author":[{"given":"Elodie","family":"Gautier-Veyret","sequence":"first","affiliation":[{"name":"Universit\u00e9 Grenoble Alpes, Grenoble, France"},{"name":"INSERM U1042, HP2, Grenoble, France"},{"name":"Laboratoire de Pharmacologie-Toxicologie, Grenoble University Hospital, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xavier","family":"Fonrose","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie-Toxicologie, Grenoble University Hospital, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julia","family":"Tonini","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie-Toxicologie, Grenoble University Hospital, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Thiebaut-Bertrand","sequence":"additional","affiliation":[{"name":"Clinique d'H\u00e9matologie, Grenoble University Hospital, Grenoble, France"},{"name":"TIMC-TheREx, UMR 5525, CNRS, La Tronche, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mireille","family":"Bartoli","sequence":"additional","affiliation":[{"name":"Laboratoire de Pharmacologie-Toxicologie, Grenoble University Hospital, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Louis","family":"Quesada","sequence":"additional","affiliation":[{"name":"D\u00e9partement Scientifique de la Direction de la Recherche Clinique et des Innovations (DRCI), Grenoble University Hospital, Grenoble, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude-Eric","family":"Bulabois","sequence":"additional","affiliation":[{"name":"Clinique d'H\u00e9matologie, Grenoble University Hospital, Grenoble, France"},{"name":"TIMC-TheREx, UMR 5525, CNRS, La Tronche, 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