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In the present study, we investigated the pharmacokinetics and toxicity of DMA and MMA in patients, mice and cell lines. In pediatric patients (6 months to 18\u2009years) undergoing hematopoietic stem cell transplantation, the pharmacokinetics of DMA and MMA were followed during the 4\u2010days Busulfex conditioning (3.2\u20134\u2009mg\/kg, b.i.d). No accumulation of DMA was found; however, a significant increase in clearance and a significant decrease (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.005) in half\u2010lives by the end of treatment were observed which might indicate CYP2E1 autoinduction. Furthermore, continuous increases in plasma concentration of MMA were observed during treatment and a terminal half\u2010life of 15.2\u2009\u00b1\u20091.7\u2009h was detected. Moreover, ALT was significantly (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.04) increased in &gt;\u200961% of the patients after conditioning. Additionally, mice were treated with either dimethyl sulfoxide (DMSO), DMA, busulphan in DMSO, Busulfex or saline for 4\u2009days. DMA\u2010treated mice showed elevated ALT and AST values. Interestingly, Busulfex administration did not alter mice liver enzymes. Busulphan in DMA showed higher cytotoxicity compared to busulphan in DMSO in HepG\u20102, Huh\u20107 and HL\u201060 cells. The combination Bu\u2010DMA\u2010MMA exhibited increased cytotoxicity in a concentration\u2010dependent manner. In conclusion, Busulfex administration to pediatric patients resulted in an accumulation of MMA during the 4\u2010days treatment. Busulfex is less toxic compared to Bu dissolved in DMA. MMA addition to Bu in DMA showed higher cytotoxicity. Therefore, MMA with a relatively long half\u2010life may induce hepatotoxicity and\/or interaction with subsequently administered drugs; thus further investigations are urgently warranted.\n                  <\/jats:p>","DOI":"10.1111\/cts.70433","type":"journal-article","created":{"date-parts":[[2025,12,2]],"date-time":"2025-12-02T12:36:05Z","timestamp":1764678965000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Pharmacokinetics and Toxicity of Dimethylacetamide and Its Metabolite in Pediatric Patients Treated With High Dose Intravenous Busulphan"],"prefix":"10.1111","volume":"18","author":[{"given":"Fadwa","family":"Benkessou","sequence":"first","affiliation":[{"name":"Experimental Cancer Medicine (ECM), Department of Laboratory Medicine Karolinska Institutet  Stockholm Sweden"},{"name":"Clinical Research Center and Center of Allogeneic Stem Cell Transplantation Karolinska University Hospital\u2010Huddinge  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