轻度营养不良是幼儿普遍存在的问题。已有观察结果表明，严重营养不良会影响小儿癌症患者的化疗药物药代动力学，但对于轻度营养不良的研究尚不充分。本研究旨在利用早期轻度营养不良的小鼠模型，了解轻度营养不良对依托泊苷和长春新碱这两种化疗药物的药代动力学的影响。 我们采用刚断奶的斯普拉格－道里（Sprague-Dawley）大鼠，通过8％蛋白质饮食喂养8个星期，建立了一种模拟儿童轻度营养不良的小鼠模型。在两个独立的实验中，我们分别对依托泊苷和长春新碱进行尾静脉注射（蛋白质缺乏组和对照组各为依托泊苷8只和长春新碱12只）以进行药代动力学研究。 我们发现，与良好营养状态下的动物相比，营养不良动物的依托泊苷的药物浓度-时间曲线下面积（AUC）增加了约60％。此外，在营养不良动物中，清除率、分布容积和半衰期分别降低了约37％、53％和24％。而长春新碱的药代动力学参数在良好营养组与营养不良组之间只有微小差异。 我们的结果表明，虽然轻度营养不良显著影响依托泊苷的药代动力学，但长春新碱的药代动力学保持不变。由于化疗药物的疗效指数较窄，我们研究中观察到的AUC差异可能解释了营养不良的小儿癌症患者依托泊苷毒性增加的原因。这为我们需要进行临床研究以验证我们的发现并为营养不良患者优化剂量提供了依据。© 2023. 作者，仅授权给Springer Nature Switzerland AG。

Moderate malnutrition is a common problem in young children. It is observed that severe malnutrition affects the pharmacokinetics of chemotherapy drugs in pediatric cancer patients, but moderate malnutrition is not well studied in this context.In this study, we aimed to understand how moderate malnutrition affects the pharmacokinetics of two chemotherapy drugs, etoposide and vincristine, using a murine model of early age moderate malnutrition.We developed a murine model of moderate childhood malnutrition by subjecting freshly weaned Sprague-Dawley rats to 8% protein diet for 8 weeks. In two separate experiments, we administered etoposide and vincristine (N = 8 for etoposide and N = 12 for vincristine each in protein deficient and control groups) through tail vein injection for pharmacokinetics study.We found ~ 60% increase in area under the concentration-time curve (AUC) of etoposide in malnourished animals as compared to well-nourished animals. Furthermore, clearance, volume of distribution, and half-life were decreased by ~ 37, 53, and 24%, respectively, in malnourished animals. Pharmacokinetic parameters of vincristine showed only marginal differences between well-nourished and malnourished groups.Our results suggest that while moderate malnutrition significantly affects the pharmacokinetics of etoposide, pharmacokinetics of vincristine remain unchanged. Since chemotherapy drugs have a narrow therapeutic index, the difference in AUC observed in our study might explain the increased toxicity of etoposide in malnourished pediatric cancer patients. This brings forth a need for robust clinical studies to validate our findings and optimize dose for malnourished patients.© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.