{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T17:29:52Z","timestamp":1748971792117},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>Therapeutic drug monitoring (TDM) for busulfan supports dose adjustment during conditioning for stem cell transplantation. The authors aimed to develop and validate limited sampling strategies (LSS) of 4\u20135 samples for a precise estimation of the area under concentration (AUC)-time curve of busulfan, in plasma as an alternative to an intensive sampling strategy (ISS) requiring 9\u201310 samples.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>ISS TDM data from 297 patients (\u226418 years of age) were used. AUC<jats:sub>LSS<\/jats:sub> was calculated using the trapezoidal rule and multiple linear regression (MLR). Unlike more complex modeling methods, MLR does not require sophisticated software or advanced training of personnel. MLR coefficients were estimated in the development subset containing randomly selected 50% of the records and were then used to calculate the AUC<jats:sub>LSS<\/jats:sub> of the remaining records (the validation subset). The agreement between dose adjustment recommendations (DAR) based on ISS and LSS, in the validation subset, was evaluated by a Bland\u2013Altman analysis. A DAR deviating from an ISS-based reference by &lt;15% was deemed acceptable.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>Twelve LSSs were acceptable. Sampling at 0, 120, 180, and 240 minutes after the start of the second infusion (LSS15) yielded the best performance, with DAR deviating from the reference by &lt;10% for 95% of cases; the AUC<jats:sub>LSS<\/jats:sub> was determined as follows: AUC<jats:sub>LSS<\/jats:sub> = 74.7954 \u00d7 C(0) + 81.8948 \u00d7 C(120) + 38.1771 \u00d7 C(180) + 138.1404 \u00d7 C(240) + 54.1837. This LSS and LSS13 performed similarly well in an independent external validation.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>MLR-based estimates of AUC<jats:sub>LSS<\/jats:sub> provide DARs that deviate minimally from the reference. LSSs allow the reduction of patient discomfort, a \u223c50% reduction of TDM-related workload for nursing staff and blood loss and a \u223c25% reduction in laboratory workload. These benefits may encourage wider use of busulfan TDM, supporting safe and efficacious personalized dosing.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1097\/ftd.0000000000000700","type":"journal-article","created":{"date-parts":[[2019,9,2]],"date-time":"2019-09-02T05:01:42Z","timestamp":1567400502000},"page":"427-434","source":"Crossref","is-referenced-by-count":8,"title":["Limited Sampling Strategies Supporting Individualized Dose Adjustment of Intravenous Busulfan in Children and Young Adults"],"prefix":"10.1097","volume":"42","author":[{"given":"Zvi","family":"Teitelbaum","sequence":"first","affiliation":[{"name":"Section of Clinical Pharmacology and Toxicology, Rambam Health Care Campus;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laila","family":"Nassar","sequence":"additional","affiliation":[{"name":"Section of Clinical Pharmacology and Toxicology, Rambam Health Care Campus;"},{"name":"The Rappaport Faculty of Medicine, Technion\u2014Israel Institute of 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