通过结直肠癌大鼠模型的药代动力学和毒代动力学评价评估奥沙利铂诱导的慢性神经病变和抗癌疗效。
Assessment of Oxaliplatin-induced Chronic Neuropathy and Anticancer Efficacy Through Pharmacokinetic and Toxicodynamic Evaluation of a Rat Model of Colorectal Cancer.
机构信息
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Kyoto, Japan.
出版信息
Anticancer Res. 2019 Aug;39(8):4207-4213. doi: 10.21873/anticanres.13581.
BACKGROUND/AIM: Oxaliplatin-induced chronic neuropathy is a prominent factor for dose reduction and not completing all cycles of chemotherapy for patients with colorectal cancer (CRC). The aim of the study was to investigate the pharmacokinetics and toxicodynamics of oxaliplatin-induced chronic neuropathy in CRC rats to ensure effective management.
MATERIALS AND METHODS
A rat model of CRC was developed using 1,2-Dimethylhydrazine and dextran sulfate. Oxaliplatin (L-OHP) was administered intravenously to CRC rats every week. The pharmacokinetic profiles and tumor distribution of L-OHP and chronic neuropathies were investigated for over four weeks.
RESULTS
The mean values of the area under the concentration-time curve for L-OHP showed a dose-dependent increase. Chronic neuropathy occurred from Day 14 in the 8 mg/kg group and Day 19 in the 3 and 5 mg/kg groups.
CONCLUSION
These results provide preliminary information for the development of a pharmacokinetic and toxicodynamic model of L-OHP for CRC therapy cycles.
背景/目的：奥沙利铂引起的慢性周围神经病是导致结直肠癌（CRC）患者减少剂量和无法完成所有化疗周期的一个重要因素。本研究旨在探讨 CRC 大鼠奥沙利铂诱导的慢性周围神经病的药代动力学和毒代动力学，以确保有效管理。
材料和方法
采用 1,2-二甲基肼和葡聚糖硫酸钠建立 CRC 大鼠模型。每周给 CRC 大鼠静脉注射奥沙利铂（L-OHP）。研究了 L-OHP 的药代动力学特征和肿瘤分布以及慢性周围神经病超过四周。
结果
L-OHP 的浓度-时间曲线下面积的平均值呈剂量依赖性增加。慢性周围神经病分别在 8mg/kg 组的第 14 天和 3mg/kg 和 5mg/kg 组的第 19 天出现。
结论
这些结果为 CRC 治疗周期 L-OHP 的药代动力学和毒代动力学模型的开发提供了初步信息。
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