{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T05:24:04Z","timestamp":1696397044701},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,1,25]],"date-time":"2017-01-25T00:00:00Z","timestamp":1485302400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81473177"],"award-info":[{"award-number":["81473177"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Invasive pulmonary aspergillosis (IPA), most caused by <jats:italic>Aspergillus fumigatus<\/jats:italic>, is a serious life\u2010threatening infection in immunocompromised patients. Voriconazole is used to prevent and treat IPA. However, little is known about the pharmacological characteristics of voriconazole in pulmonary epithelial cells, which are the target site for the prophylaxis and early treatment of IPA. The aim of the study was to evaluate the kinetics and activity of voriconazole against <jats:italic>A. fumigatus<\/jats:italic> in A549 cells. High\u2010performance liquid chromatography\/tandem mass spectrometry and time\u2010kill method were used to study the cellular pharmacokinetic and pharmacodynamics of voriconazole. Voriconazole exerted a concentration\u2010dependent toxic effect on A549 cells and could penetrate into cells, reaching plateau concentrations of 1.14 \u00b1 0.64, 3.72 \u00b1 1.38 and 6.36 \u00b1 0.95 ng\/mg protein after A549 cells were exposed to voriconazole at extracellular concentrations of 2, 8 and 16 mg\/L for 2 h, respectively. The efflux of voriconazole was rapid, with a half\u2010life of 10.2 min. Voriconazole can decrease the <jats:italic>A. fumigatus<\/jats:italic> conidia invade cells, and the number of viable <jats:italic>A. fumigatus<\/jats:italic> conidia in cells can be decreased 2.1\u2010 to 20.6\u2010fold when A549 cells were cultured in medium containing voriconazole. After 24\u2010h incubation, 75.6% and 80.5% of intracellular <jats:italic>A. fumigatus<\/jats:italic> were killed when extracellular voriconazole concentration was 8 and 16 mg\/L, respectively. This study illustrated a new application for the prophylaxis and early treatment of IPA from the cellular pharmacokinetics and pharmacodynamics and emphasized the importance of monitoring concentrations of voriconazole in epithelial lining fluid in immunocompromised patients receiving voriconazole therapy.<\/jats:p>","DOI":"10.1111\/fcp.12262","type":"journal-article","created":{"date-parts":[[2016,12,25]],"date-time":"2016-12-25T04:53:29Z","timestamp":1482641609000},"page":"311-318","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Uptake and efflux kinetics, and intracellular activity of voriconazole against <i>Aspergillus fumigatus<\/i> in human pulmonary epithelial cells: a new application for the prophylaxis and early treatment of invasive pulmonary aspergillosis"],"prefix":"10.1111","volume":"31","author":[{"given":"Taotao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qianting","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ti","family":"Meng","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jin'e","family":"Lei","sequence":"additional","affiliation":[{"name":"Department of Laboratory The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianfeng","family":"Xing","sequence":"additional","affiliation":[{"name":"School of Pharmacy Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yalin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Pharmacy The First Affiliated Hospital of Xi'an Jiaotong University Xi'an 710061 China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2017,1,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00425-10"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.seminhematol.2009.03.003"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.blre.2009.11.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00055-08"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00133-06"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2009.02913.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1086\/653683"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.2165\/00003088-200645070-00002"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12212"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2014.07.013"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkt369"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12230"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-6143.2010.03375.x"},{"key":"e_1_2_9_15_1","doi-asserted-by":"crossref","first-page":"3008","DOI":"10.1111\/j.1600-6143.2006.01548.x","article-title":"Voriconazole prophylaxis in lung transplant recipients","volume":"12","author":"Husain S.","year":"2006","journal-title":"Am. 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