{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T20:57:14Z","timestamp":1781557034508,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T00:00:00Z","timestamp":1732060800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Brit J Clinical Pharma"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p>To evaluate the effectiveness of a Bayesian adaptive dosing strategy in achieving target busulfan exposure in adult patients undergoing haematopoietic cell transplantation (HCT).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study included 71 adult patients scheduled to receive high\u2010dose busulfan. Busulfan was administered to achieve a cumulative area under the curve (AUC) of 66.0\u00a0mg.h\/L (16\u2009000\u2009\u03bcM.min), 82.60\u2009mg.h\/L (20\u2009000\u2009\u03bcM.min) or 87.6 mg.h\/L (21\u2009200\u2009\u03bcM.min) depending on the regimen. Individual pharmacokinetic (PK) parameters of busulfan were estimated from three blood samples using a one\u2010compartment model and Bayesian estimation after the first standard dose. Individual PK parameters were used to adjust subsequent doses to achieve the target exposure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All patients had their dose adjusted after the first dose administration. The final deviation from the target AUC was significantly improved compared to the initial deviation after standard mg\/kg dosing (mean absolute deviation 19.5% <jats:italic>vs<\/jats:italic> 11.7%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.01). In addition, the proportion of patients with marked deviation from target exposure (ie, &gt;25%) decreased significantly from 31% after standard dosing to 10% after PK\u2010guided dosing (<jats:italic>P<\/jats:italic>\u00a0&lt;\u2009.01). Canonical busulfan\u2010related toxicity, specifically veno\u2010occlusive disease, was observed in 5% of patients who achieved successful PK\u2010guided dosing. In contrast, one\u2010third of patients with off\u2010target exposure with poor dosing experienced toxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>The Bayesian adaptive dosing strategy significantly improves the accuracy of achieving the target busulfan AUC in patients undergoing HCT. This approach not only reduces marked deviations from target exposure, but also reduces the incidence of busulfan\u2010related toxicity, thereby maintaining a favourable toxicity\/efficacy ratio.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bcp.16343","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:48:11Z","timestamp":1732096091000},"page":"1171-1181","source":"Crossref","is-referenced-by-count":5,"title":["Adaptive dosing of high\u2010dose busulfan in real\u2010world adult patients undergoing haematopoietic cell transplant conditioning"],"prefix":"10.1111","volume":"91","author":[{"given":"Dorian","family":"Protzenko","sequence":"first","affiliation":[{"name":"COMPO, Inserm U1068 Centre de Recherche en Canc\u00e9rologie de Marseille Aix Marseille University  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin","family":"Bouchacourt","sequence":"additional","affiliation":[{"name":"HematologyDepartment Paoli 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