{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:51:51Z","timestamp":1791971511069,"version":"4.3.4"},"reference-count":25,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["accp1.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Clinical Pharma"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Busulfan, used in hematopoietic stem cell transplantation, exhibits a narrow therapeutic index and high pharmacokinetic (PK) variability. Therapeutic drug monitoring (TDM) is currently employed to achieve target exposure. However, there is no consensus on an optimal limited sampling strategy (LSS) for busulfan on the once\u2010daily (QD) regimen. A virtual cohort of adult patients (n\u00a0=\u00a01000) receiving OD intravenous busulfan 3.2\u00a0mg\/kg as a 3\u2010h infusion was generated by Monte Carlo simulation using three published busulfan population PK models. For each one\u2010 and two\u2010sample LSS, individual PK parameters were estimated from Day\u20101 sample(s) by maximum a posteriori Bayesian estimation and used to estimate the 4\u2010day cumulative AUC. A model\u2010informed precision\u2010dosing (MIPD) analysis quantified the target\u2010attainment benefit of TDM per design. The best\u2010performing designs were validated in an external cohort (n\u00a0=\u00a037) with adults and adolescents. Across all three models, a two\u2010sample early\u2010plus\u2010late schedule was the most informative, and the recommended two\u2010sample design was 3 and 7\u00a0h after the start of infusion. TDM guided by a well\u2010chosen LSS approximately doubled cumulative\u2010target attainment, whereas a single early 3\u2010h sample was markedly weaker. In the external cohort, two\u2010sample designs recovered the cumulative 4\u2010day AUC to \u223c5%\u20138% MAPE versus \u223c11%\u201313% for a single 3\u2010h sample. For OD intravenous busulfan in adults and adolescents, a two\u2010sample schedule at 3 and 7\u00a0h after the start of infusion supports the correct dosing decision and, through MIPD\u2010guided dose adjustment, approximately doubles target attainment; a single 6\u2010h sample is a simpler but less robust alternative.<\/jats:p>","DOI":"10.1002\/jcph.70281","type":"journal-article","created":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T18:18:08Z","timestamp":1788286688000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Simulation\u2010Based Evaluation of Busulfan Sampling Strategies in Adults and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplantation"],"prefix":"10.1002","volume":"66","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2681-6932","authenticated-orcid":false,"given":"Zhiyuan","family":"Tan","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacy &amp; Toxicology Leiden University Medical Center  Leiden The Netherlands"},{"name":"Division of Systems Pharmacology and Pharmacy Leiden Academic Center for Drug Research Leiden University  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Federica R.","family":"Achini\u2010Gutzwiller","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arjan C.","family":"Lankester","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joost G. K.","family":"van der Hem","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A.","family":"von dem Borne","sequence":"additional","affiliation":[{"name":"Department of Hematology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3219-253X","authenticated-orcid":false,"given":"Dirk Jan. A. R.","family":"Moes","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy &amp; Toxicology Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6953-0358","authenticated-orcid":false,"given":"Tim","family":"Preijers","sequence":"additional","affiliation":[{"name":"Department of Hospital Pharmacy Rotterdam Erasmus Medical Center  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,1]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/nejm198312013092202"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2008.12.489"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2019.09.008"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/1078155214541571"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010020\u201000877\u2010z"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/s2352\u20103026(16)30114\u20104"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtct.2024.07.015"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010020\u201000947\u20102"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41409\u2010023\u201001971\u2010z"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.2174\/138161208785061382"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbmt.2016.07.013"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00280\u2010019\u201004006\u2010x"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010013\u20100124\u2010z"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095\u2010013\u20101079\u20103"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1540139"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1053\/bbmt.2002.v8.abbmt080619"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10928\u2010024\u201009929\u20104"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.Ccr\u201013\u20101960"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bmt.1705252"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3748"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1097\/ftd.0000000000001126"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.29069"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/ftd.0000000000001217"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0169\u20107439(94)00076\u2010X"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262\u2010023\u201001275\u2010x"}],"container-title":["The Journal of Clinical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70281","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcph.70281","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcph.70281","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T09:20:39Z","timestamp":1791969639000},"score":1,"resource":{"primary":{"URL":"https:\/\/accp1.onlinelibrary.wiley.com\/doi\/10.1002\/jcph.70281"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9]]},"references-count":25,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2026,9]]}},"alternative-id":["10.1002\/jcph.70281"],"URL":"https:\/\/doi.org\/10.1002\/jcph.70281","archive":["Portico"],"relation":{},"ISSN":["0091-2700","1552-4604"],"issn-type":[{"value":"0091-2700","type":"print"},{"value":"1552-4604","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9]]},"assertion":[{"value":"2026-05-20","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70281"}}