A study to explore the correlation of ABCB1, ABCG2, OCT1 genetic polymorphisms and trough level concentration with imatinib mesylate-induced thrombocytopenia in chronic myeloid leukemia patients
A study to explore the correlation of ABCB1, ABCG2, OCT1 genetic polymorphisms and trough level concentration with imatinib mesylate-induced thrombocytopenia in chronic myeloid leukemia patients
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DOI：
10.1007/s00280-015-2905-6
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发表时间：
2015-12-01
影响因子：
3
通讯作者：
Chandrasekaran, Adithan
中科院分区：
文献类型：
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作者：
Francis, Jose;Dubashi, Biswajit;Chandrasekaran, Adithan
甲磺酸伊马替尼是目前治疗慢性粒细胞白血病（CML）的一线药物。治疗药物监测（TDM）和药物遗传学筛查是必要的，以更好地管理伊马替尼治疗。本研究旨在探讨常见药物转运蛋白基因ABCB 1、ABCG 2、OCT 1多态性及谷浓度对甲磺酸伊马替尼治疗慢性期CML患者常见不良事件的影响，共纳入111例慢性期（费城染色体+ve）患者。采用LC-MS/MS法测定伊马替尼的血药浓度，平均+/- A SD谷浓度为1430.7 +/- A 438.7 ng/ml。2-4级血小板减少患者的稳态谷浓度（Cmin. ss）显著高于无不良事件的患者（P值0.033），伊马替尼血药浓度与血小板减少的严重程度相关，增加了TDM在CML患者治疗中的应用价值。
Imatinib mesylate is presently the first-line treatment for chronic myeloid leukemia (CML). Therapeutic drug monitoring (TDM) and pharmacogenetic screening is warranted for better management of imatinib therapy. The present study was framed to explore the influence of common drug transporter gene polymorphisms of ABCB1, ABCG2, OCT1 and trough level concentration on commonly occurring adverse events in CML patients treated with imatinib mesylate.A total number of 111 patients in chronic phase (Philadelphia chromosome +ve) were included in the study. The plasma drug concentration of imatinib was estimated using LC-MS/MS method.The mean +/- A SD trough level concentration of imatinib mesylate was found to be 1430.7 +/- A 438.7 ng/ml. The trough level concentration at steady state (Cmin.ss) was significantly higher in patients with grade 2-4 thrombocytopenia compared with patients without the adverse event (P value 0.033).The drug level of imatinib in plasma correlates with the severity of thrombocytopenia, which adds to the utility of TDM in the management of CML patients.