{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T19:53:22Z","timestamp":1789502002499,"version":"build-2803163510"},"reference-count":17,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2021,4,21]],"date-time":"2021-04-21T00:00:00Z","timestamp":1618963200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2021,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Therapeutic drug monitoring for busulfan is important to prevent adverse events and improve outcomes in stem cell transplantation. We investigated intravenous busulfan pharmacokinetics and evaluated the utility of limited sampling strategy (LSS) as a simple method to estimate the area under the concentration\u2010time curve (AUC).<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>The study comprised 87 busulfan measurements in 54 children who received intravenous busulfan between August 2015 and May 2020. AUCs were calculated from three to five blood sampling points in each patient, and the correlation between AUC and plasma concentrations (ng\/mL) at 1, 2, 3, 4, and 6 h after initiating busulfan infusion (C<jats:sub>1<\/jats:sub>, C<jats:sub>2<\/jats:sub>, C<jats:sub>3<\/jats:sub>, C<jats:sub>4<\/jats:sub>, and C<jats:sub>6<\/jats:sub>, respectively).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>By one\u2010point sampling strategy, the most relevant predicted AUC was based on C<jats:sub>6<\/jats:sub> (<jats:italic>r<jats:sup>2<\/jats:sup><\/jats:italic>\u00a0=\u00a00.789; precision, 11.0%) in all patients. The predicted AUC based on C<jats:sub>6<\/jats:sub> was acceptable (<jats:italic>r<jats:sup>2<\/jats:sup><\/jats:italic>\u00a0=\u00a00.937; precision, 5.9%) for adolescent patients weighing\u00a0&gt;23\u00a0kg, but the correlation was poor in infants and young children weighing \u2264 23\u00a0kg (<jats:italic>r<jats:sup>2<\/jats:sup><\/jats:italic>\u00a0=\u00a00.782; precision, 11.4%). By two\u2010point sampling strategy, the predicted AUC based on C<jats:sub>3<\/jats:sub> and C<jats:sub>6<\/jats:sub> showed the most relevant concentrations (<jats:italic>r<jats:sup>2<\/jats:sup><\/jats:italic>\u00a0=\u00a00.943; precision, 6.4%), even in infants and young children, whereas the predicted AUC based on C<jats:sub>3<\/jats:sub> and C<jats:sub>6<\/jats:sub> was acceptable (<jats:italic>r<jats:sup>2<\/jats:sup><\/jats:italic>\u00a0=\u00a00.963; precision, 5.7%).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The AUC of busulfan can be predicted based on C<jats:sub>6<\/jats:sub> in adolescent patients. However, there was substantial interindividual variation in busulfan pharmacokinetics in infants and young children, in whom two\u2010point LSS was necessary for accurate AUC prediction.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29069","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T01:20:16Z","timestamp":1619054416000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Two\u2010point blood sampling is sufficient and necessary to estimate the area under the concentration\u2010time curve for intravenous busulfan in infants and young children"],"prefix":"10.1002","volume":"68","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1373-9122","authenticated-orcid":false,"given":"Tomoyuki","family":"Utano","sequence":"first","affiliation":[{"name":"Department of Pharmaceuticals National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motohiro","family":"Kato","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5536-6788","authenticated-orcid":false,"given":"Tomoo","family":"Osumi","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kana","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences Doshisha Women's College of Liberal Arts  Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1520-7007","authenticated-orcid":false,"given":"Daisuke","family":"Tomizawa","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-3781","authenticated-orcid":false,"given":"Kimikazu","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Children's Cancer Center National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akimasa","family":"Yamatani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceuticals National Center for Child Health and Development  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,4,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)30114-4"},{"issue":"2","key":"e_1_2_9_3_1","first-page":"225","article-title":"Association of busulfan area under the curve with veno\u2010occlusive disease following BMT","volume":"17","author":"Dix SP","year":"1996","journal-title":"Bone Marrow Transplant"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-3046.2011.01529.x"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(13)62069-3"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705240"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-13-1960"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1704446"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.07.008"},{"key":"e_1_2_9_10_1","volume-title":"Evaluation and Licensing Division. 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