中度营养不良对新断奶大鼠足叶乙甙和长春新碱药代动力学的影响。

IF 1.9 4区 医学 Q3 PHARMACOLOGY & PHARMACY
Megha Garg, Khushboo Gandhi, Shraddha Mahesh Jadhav, Murari Gurjar, Vikram Gota
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引用次数: 0

摘要

背景:中度营养不良是幼儿的常见问题。据观察,严重营养不良影响癌症儿童患者化疗药物的药代动力学,但中度营养不良在这方面的研究尚不充分。目的:在本研究中,我们旨在利用早期中度营养不良的小鼠模型,了解中度营养不良如何影响依托泊苷和长春新碱两种化疗药物的药代动力学。方法:我们通过对刚断奶的Sprague-Dawley大鼠进行8%蛋白质饮食8周,建立了中度儿童营养不良的小鼠模型。在两个单独的实验中,我们给药依托泊苷和长春新碱(N = 依托泊苷和N为8 = 蛋白质缺乏组和对照组各12个长春新碱)通过尾静脉注射进行药代动力学研究。结果:我们发现~ 与营养良好的动物相比,营养不良的动物中依托泊苷的浓度-时间曲线下面积(AUC)增加了60%。此外,清除率、分布体积和半衰期减少了~ 在营养不良的动物中分别为37%、53%和24%。长春新碱的药代动力学参数在营养良好组和营养不良组之间仅显示出微小差异。结论:我们的研究结果表明,虽然中度营养不良会显著影响依托泊苷的药代动力学,但长春新碱的药代学保持不变。由于化疗药物的治疗指数较窄,我们研究中观察到的AUC差异可能解释了依托泊苷对营养不良的癌症儿童患者毒性增加的原因。这就需要强有力的临床研究来验证我们的发现,并优化营养不良患者的剂量。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Effect of Moderate Malnutrition on the Pharmacokinetics of Etoposide and Vincristine in Freshly Weaned Rats.

Effect of Moderate Malnutrition on the Pharmacokinetics of Etoposide and Vincristine in Freshly Weaned Rats.

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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来源期刊
CiteScore
3.70
自引率
0.00%
发文量
64
审稿时长
>12 weeks
期刊介绍: Hepatology International is a peer-reviewed journal featuring articles written by clinicians, clinical researchers and basic scientists is dedicated to research and patient care issues in hepatology. This journal focuses mainly on new and emerging diagnostic and treatment options, protocols and molecular and cellular basis of disease pathogenesis, new technologies, in liver and biliary sciences. Hepatology International publishes original research articles related to clinical care and basic research; review articles; consensus guidelines for diagnosis and treatment; invited editorials, and controversies in contemporary issues. The journal does not publish case reports.
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