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Pharmacokinetics and Toxicity of Dimethylacetamide and Its Metabolite in Pediatric Patients Treated With High Dose Intravenous Busulphan.


ABSTRACT: N,N-dimethylacetamide (DMA) is an organic solvent, used in busulphan, iv-formulation, (Busulfex). DMA is metabolized primarily to N-methylacetamide (MMA) via CYP2E1. 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 years) undergoing hematopoietic stem cell transplantation, the pharmacokinetics of DMA and MMA were followed during the 4-days Busulfex conditioning (3.2-4 mg/kg, b.i.d). No accumulation of DMA was found; however, a significant increase in clearance and a significant decrease (p < 0.005) in half-lives by the end of treatment were observed which might indicate CYP2E1 autoinduction. Furthermore, continuous increases in plasma concentration of MMA were observed during treat

SUBMITTER: Benkessou F 

PROVIDER: S-EPMC12670296 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature