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Review Article

伊立替康毒性的药代动力学和药物遗传学标记

卷 26, 期 12, 2019

页: [2085 - 2107] 页: 23

弟呕挨: 10.2174/0929867325666180622141101

价格: $65

摘要

背景：伊立替康（IRI）是一种广泛使用的化学治疗药物，主要用于结直肠癌和胰腺癌的一线治疗。 IRI剂量通常基于患者的体表面积来确定，该方法与药物暴露的大的个体间可变性和严重毒性的高发生率相关。 IRI的毒性和治疗效果也归因于其活性代谢物SN-38，据报道其细胞毒性比IRI高100倍。 SN-38通过UGT1A1形成SN-38葡糖苷酸而被解毒。 UGT1A1基因的遗传多态性与较高的SN-38暴露和严重毒性有关。可用于描述IRI和SN-38动力学曲线的药代动力学模型，很少有研究探索药代动力学和基于药物遗传学的剂量个体化。本手稿的目的是审查支持药物遗传学和药代动力学剂量个体化IRI的现有证据，以减少癌症治疗期间严重毒性的发生。 方法：检索PubMed数据库，考虑1995 - 2017年期间发表的论文，使用关键词伊立替康，药物遗传学，代谢基因分型，剂量个体化，治疗药物监测，药代动力学和药效学，单独或组合使用，原始论文为根据相关数据的存在选择。 结论：本综述的结果证实了考虑个体患者特征选择IRI剂量的重要性。目前，IRI剂量个体化最直接的方法是UGT1A1基因分型。然而，由于对IRI及其活性代谢物的可变药代动力学的若干其他遗传和环境贡献，该策略是次优的。干血斑取样的使用可以允许临床应用有限的取样和群体药代动力学模型用于IRI剂量个体化。

关键词: 伊立替康，SN-38，药代动力学，药物遗传学，剂量个体化，UGT1A1基因分型。

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