慢性粒细胞白血病患者血浆伊马替尼浓度检测与临床疗效分析

Detection of imatinib in the plasma and its effect in the patient with chronic myeloid leukemia

目的探讨慢性粒细胞白血病（CML）患者服用伊马替尼治疗后，伊马替尼血浆浓度在个体间的差异以及与临床疗效的关系。方法2005年7月至2008年2月开始服用伊马替尼治疗的CML患者共51例纳入研究，其中男34例，女17例，服用剂量300mg／d9例、400mg／d37例，600mg／d5例；采用高效液相色谱法（HPLC）测定患者空腹伊马替尼血浆谷浓度；SPSSl3．0软件进行统计分析。结果伊马替尼血浆谷浓度与服用剂量有关，且个体之间差异较大，为（342～4688）ng／ml；300ITIg／d剂量组的伊马替尼血浆谷浓度为（1037±514）ng／ml，低于400mg／d剂量组的（2123±1016）11g／ml（t=2．34，P=0．032）；300mg／d剂量组的治疗有效率为66．67％（6／9），低于400mg／d剂量组的89．19％（33／37）（X^2=7．14，／9=0．008）；在300、400mg／d剂量组中，39例治疗有效，伊马替尼血浆谷浓度高于治疗效果不理想患者，差异有统计学意义（t=2．25，P=0．037）；受试者工作特征曲线（ROC曲线）结果提示伊马替尼血浆谷浓度低于1050ng／ml者，其临床疗效可能较差，敏感度为84．6％，特异度为71．1％。结论CML患者服用伊马替尼治疗后药物血浆浓度与服用剂量有关，不同个体间差异较大，血浆谷浓度低于1050ng／ml提示其临床疗效可能较差。

Objective To evaluate the relationship between plasma imatinib and its effect in the treatment of chronic myeloid leukemia（CML）. Methods Fifty-one CML patients were included in this study, who began taking imatinib from July 2005 to February 2008, with 34 cases of male, and 17 cases of female. Nine patients took imatinib at dose of 300mg/d, 37 patients took imatinib at dose of 400mg/d, and 5 patients took imatinib at dose of 600 mg/d. High-performance liquid chromatography was used to test imatinib plasma levels. Results The imatinib plasma levels was imatinib dose-related, and the imatinib plasma trough levels significantly varied between individuals[（342-4688）ng/ml]. The imatinib plasma levels was significant lower in 300 mg/d dose group [（1037±514） ng/ml] than 400 mg/d dose group [（2123±1016） ng/ml] （t =2.34, P =0.032）, and the effective rate was 66.7 % （6/9） in 300 mg/d dose group, which was lower than 400 mg/d dose group of 89.19 % （33/37） （X^2=7.14, P =0.008）. In 300 mg/d and 400 mg/d dose groups, 39 patients achieved effective treatment, and their imatinib plasma levels was significant higher than that of 7 patients who did not achieved effective treatment （t =2.25, P =0.037）. The ROC curve results suggested that clinical treatment may be poor when the imatinib plasma level was lower than 1050 ng/ml （sensitivity was 84.6 %, specificity was 71.1%）. Conclusion The imatinib plasma levels was dose-related, and significantly varied between individuals. Clinical treatment effect may be poor when the imatinib plasma level was lower than 1050 ng/ml.