{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:47:40Z","timestamp":1791503260481,"version":"4.3.4"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2017,11,22]],"date-time":"2017-11-22T00:00:00Z","timestamp":1511308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2017,12,1]],"date-time":"2017-12-01T00:00:00Z","timestamp":1512086400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100004324","name":"Astellas Pharma US","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004324","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Basilea Pharmaceutica International Ltd."}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Quantitative whole-body autoradiography was used to assess the distribution and tissue penetration of isavuconazole in rats following single and repeated oral-dose administration of radiolabeled isavuconazonium sulfate, the prodrug of isavuconazole. Following a single-dose administration of radiolabeled isavuconazonium sulfate (labeled on the active moiety), radioactivity was detectable within 1 h postdose in 56 of 65 tissue\/fluid specimens. The highest maximum concentrations (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>) were observed in bile and liver (66.6 and 24.7 \u03bcg eq\/g, respectively). The lowest<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>values were in bone and eye lens (0.070 and 0.077 \u03bcg eq\/g, respectively). By 144 h postdose, radioactivity was undetectable in all tissues\/fluids except liver (undetectable at 336 h) and adrenal gland tissues (undetectable at 672 h). Following daily administration for up to 21 days, 1-h-postdose<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>values were the highest on or before day 14 in all except seven tissues\/fluids, of which only rectum mucosa and small intestine mucosa had<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>values &gt;25% higher than all other 1-h-postdose values. For 24-h-postdose<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>values, only large intestine, large intestine mucosa, and urine had the highest<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>values at day 21. The penetration of single oral doses of unlabeled isavuconazole (25 mg\/kg of body weight isavuconazonium sulfate) and voriconazole (50 mg\/kg) into rat brain (assessed using liquid chromatography-tandem mass spectrometry) was also compared. Brain concentration\/plasma concentration ratios reached approximately 1.8:1 and 2:1, respectively. These data suggest that isavuconazole penetrates most tissues rapidly, reaches a steady state in most or all tissues\/fluids within 14 days, does not accumulate in tissues\/fluids over time, and achieves potentially efficacious concentrations in the brain.<\/jats:p>","DOI":"10.1128\/aac.01292-17","type":"journal-article","created":{"date-parts":[[2017,10,3]],"date-time":"2017-10-03T00:30:26Z","timestamp":1506990626000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":70,"title":["Tissue Distribution and Elimination of Isavuconazole following Single and Repeat Oral-Dose Administration of Isavuconazonium Sulfate to Rats"],"prefix":"10.1128","volume":"61","author":[{"given":"Anne-Hortense","family":"Schmitt-Hoffmann","sequence":"first","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kota","family":"Kato","sequence":"additional","affiliation":[{"name":"Analysis &amp; Pharmacokinetics Research Laboratories, Astellas Pharma Inc., Osaka, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Townsend","sequence":"additional","affiliation":[{"name":"Astellas Pharma Global Development, Inc., Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Potchoiba","sequence":"additional","affiliation":[{"name":"Covance Laboratories, Inc., Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6187-878X","authenticated-orcid":false,"given":"William W.","family":"Hope","sequence":"additional","affiliation":[{"name":"University of Liverpool, Liverpool, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Andes","sequence":"additional","affiliation":[{"name":"University of Wisconsin, Madison, Wisconsin, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Spickermann","sequence":"additional","affiliation":[{"name":"Basilea Pharmaceutica International Ltd., Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7117-5199","authenticated-orcid":false,"given":"Marlowe J.","family":"Schneidkraut","sequence":"additional","affiliation":[{"name":"Astellas Research Institute of America, Northbrook, Illinois, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1086\/651263"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/649879"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00046-13"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.3.4.573"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.39.5.1154"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl141"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.48.3.815-823.2004"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00949-10"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkl396"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-015-0398-6"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/civ571"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1177\/1060028015581679"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki399"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01355-13"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01354-13"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02301-13"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn431"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02665-15"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.04907-14"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(15)01159-9"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(16)00071-2"},{"key":"e_1_3_2_23_2","volume-title":"Abstr 27th Eur Congr Clin Microbiol Infect Dis","author":"Larger P","year":"2017","unstructured":"Larger P WenzlerU Schmitt-HoffmannA. 2017. 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