Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.
Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Suez Canal University, Ismailia, Egypt.
Bone Marrow Transplant. 2021 Apr;56(4):807-817. doi: 10.1038/s41409-020-01091-y. Epub 2020 Oct 21.
Vitamin D (Vit-D), an essential nutrient, interacts with different drugs including chemotherapeutic agents like busulphan, an alkylating agent used for conditioning prior to stem cell transplantation. The correlation between Vit-D plasma levels and busulphan clearance was investigated in an uncontrolled prospective study in patients and mice. Plasma 25(OH)D levels were measured and busulphan pharmacokinetics calculated in 81 patients. Adults received oral busulphan (n = 34) while children received busulphan orally (n = 19) or intravenously (n = 28). Patients received no Vit-D supplementation. To confirm our findings, pharmacokinetics after a single dose of busulphan (oral or intravenous) were evaluated in two groups of mice (n = 60) receiving high or standard-level Vit-D supplementation. Both busulphan clearance (P < 0.0001) and 25(OH)D levels (P = 0.0004) were significantly higher in adults compared to children. A significant negative correlation (P = 0.041) was found between busulphan clearance and 25(OH)D levels in children treated orally. No such correlation was observed in adults or in children receiving intravenous busulphan. In addition, no significant effect of Vit-D levels on busulphan pharmacokinetics in mice regardless of the administration route. In conclusion, 25(OH)D can affect oral busulphan pharmacokinetics in children and its level should be considered when personalizing oral busulphan treatment. Further studies are warranted to confirm the underlying mechanisms.
维生素 D（Vit-D）是一种必需营养素，与不同的药物相互作用，包括烷化剂如白消安，白消安用于干细胞移植前的预处理。在一项针对患者和小鼠的非对照前瞻性研究中，研究了 Vit-D 血浆水平与白消安清除率之间的相关性。在 81 名患者中测量了血浆 25（OH）D 水平并计算了白消安药代动力学。成人接受口服白消安（n=34），儿童接受口服（n=19）或静脉注射（n=28）白消安。患者未接受 Vit-D 补充。为了证实我们的发现，在接受高或标准水平 Vit-D 补充的两组小鼠（n=60）中评估了单次口服或静脉注射白消安后的药代动力学。与儿童相比，成人的白消安清除率（P<0.0001）和 25（OH）D 水平（P=0.0004）均显著更高。在接受口服治疗的儿童中，发现白消安清除率与 25（OH）D 水平之间存在显著负相关（P=0.041）。在接受静脉注射白消安的成人或儿童中未观察到这种相关性。此外，无论给药途径如何，Vit-D 水平对白消安药代动力学均无显著影响。结论：25（OH）D 可影响儿童口服白消安的药代动力学，在个性化口服白消安治疗时应考虑其水平。需要进一步的研究来证实潜在的机制。
