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[伊马替尼治疗药物监测在肿瘤学中的潜在临床益处]

[Potential clinical benefit of therapeutic drug monitoring of imatinib in oncology].

作者信息

Turjap M, Juřica J, Demlová R

出版信息

Klin Onkol. 2015;28(2):105-11. doi: 10.14735/amko2015105.

Abstract

Imatinib mesylate is a competitive inhibitor of BCR/ ABL tyrosine kinase and inhibits also several receptor tyrosin kinases. Since its launch to the market, imatinib has proven to be very valuable in the treatment of Philadelphia chromosome (BCR/ ABL) -  positive (Ph+) chronic myeloid leukemia and Kit (CD117) positive gastrointestinal stromal tumors. The drug is metabolized by cytochrome P450, and there are many clinically important pharmacokinetic drug-drug interactions described in the literature. Frequent polypharmacy in oncological patients increases probability of such interactions, and also adherence may play its role during longterm treatment. Fixed dosing therapeutic regimens fail to respect known interindividual variability in pharmacokinetics of the drug and thus, some patients may not achieve sufficient plasma concentrations. Based on current evidence, there seems to be a relationship between plasma concentration and clinical response to imatinib. Therefore, imatinib appears to be suitable candidate for therapeutic drug monitoring. Here, we present an overview of pharmacokinetics, drug-drug interactions and current knowledge and suggestions on therapeutic drug monitor-ing of imatinib, its potential benefits and limitations.

摘要

甲磺酸伊马替尼是一种BCR/ABL酪氨酸激酶的竞争性抑制剂,同时也能抑制多种受体酪氨酸激酶。自上市以来,伊马替尼已被证明在治疗费城染色体(BCR/ABL)阳性(Ph+)慢性髓性白血病和Kit(CD117)阳性胃肠道间质瘤方面具有极高价值。该药物通过细胞色素P450进行代谢,文献中描述了许多具有临床重要性的药代动力学药物相互作用。肿瘤患者中频繁的联合用药增加了此类相互作用的可能性,而且在长期治疗过程中依从性也可能发挥作用。固定剂量的治疗方案未能考虑到该药物药代动力学中已知的个体间差异,因此,一些患者可能无法达到足够的血浆浓度。基于目前的证据,血浆浓度与伊马替尼的临床反应之间似乎存在关联。因此,伊马替尼似乎是治疗药物监测的合适候选药物。在此,我们概述了伊马替尼的药代动力学、药物相互作用以及当前关于其治疗药物监测的知识和建议、潜在益处和局限性。

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