Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics.
Individualization of Irinotecan Treatment: A Review of Pharmacokinetics, Pharmacodynamics, and Pharmacogenetics.
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DOI：
10.1007/s40262-018-0644-7
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发表时间：
2018-10
影响因子：
4.5
通讯作者：
Bins S
中科院分区：
文献类型：
--
作者：
de Man FM;Goey AKL;van Schaik RHN;Mathijssen RHJ;Bins S
自1998年临床引入以来，拓扑异构酶I抑制剂伊立替康已广泛用于治疗实体瘤，包括结直肠癌、胰腺癌和肺癌。伊立替康治疗的特征是几种剂量限制性毒性和较大的个体间药代动力学变异性。伊立替康具有高度复杂的代谢，包括通过羧酸酯酶水解为其活性代谢产物SN-38，SN-38的活性是伊立替康本身的100- 1000倍。几种I相和II相酶，包括细胞色素P450（CYP）3A 4和尿苷二磷酸葡萄糖醛酸转移酶（UGT）1A，参与形成无活性代谢物，使其代谢容易受到环境和遗传影响。这些酶和转运蛋白的DNA中的遗传变异可以预测药物相关毒性和治疗效果的一部分，这已在回顾性和前瞻性试验和荟萃分析中显示。患者特征、生活方式和合并用药也影响伊立替康的药代动力学。目前正在研究其他因素，包括饮食限制。与此同时，需要一种更有针对性的方法来防止过度毒性和优化疗效。本文综述了伊立替康的药代动力学、药效学和药物遗传学的最新文献。
Since its clinical introduction in 1998, the topoisomerase I inhibitor irinotecan has been widely used in the treatment of solid tumors, including colorectal, pancreatic, and lung cancer. Irinotecan therapy is characterized by several dose-limiting toxicities and large interindividual pharmacokinetic variability. Irinotecan has a highly complex metabolism, including hydrolyzation by carboxylesterases to its active metabolite SN-38, which is 100- to 1000-fold more active compared with irinotecan itself. Several phase I and II enzymes, including cytochrome P450 (CYP) 3A4 and uridine diphosphate glucuronosyltransferase (UGT) 1A, are involved in the formation of inactive metabolites, making its metabolism prone to environmental and genetic influences. Genetic variants in the DNA of these enzymes and transporters could predict a part of the drug-related toxicity and efficacy of treatment, which has been shown in retrospective and prospective trials and meta-analyses. Patient characteristics, lifestyle and comedication also influence irinotecan pharmacokinetics. Other factors, including dietary restriction, are currently being studied. Meanwhile, a more tailored approach to prevent excessive toxicity and optimize efficacy is warranted. This review provides an updated overview on today’s literature on irinotecan pharmacokinetics, pharmacodynamics, and pharmacogenetics.
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影响因子：
3
作者：
Allegrini, Giacomo;Di Paolo, Antonello;Falcone, Alfredo
通讯作者：
Falcone, Alfredo
影响因子：
3
作者：
Brell, Joanna M.;Krishnamurthi, Smitha S.;Remick, Scot C.
通讯作者：
Remick, Scot C.
影响因子：
3
作者：
Ramirez, Jacqueline;Wu, Kehua;Janisch, Linda;Karrison, Theodore;House, Larry K.;Innocenti, Federico;Cohen, Ezra E. W.;Ratain, Mark J.
通讯作者：
Ratain, Mark J.
影响因子：
2.6
作者：
Barbarino JM;Haidar CE;Klein TE;Altman RB
通讯作者：
Altman RB
DOI：
10.1073/pnas.95.14.8170
发表时间：
1998-07-07
影响因子：
11.1
作者：
Beutler, E;Gelbart, T;Demina, A
通讯作者：
Demina, A