我国慢性髓系白血病患者服用伊马替尼血药浓度的初步分析

Analysis of plasma trough level of imatinib in Chinese CML patients

目的评价我国慢性髓系白血病（CML）患者接受伊马替尼治疗的血浆谷浓度水平，以及伊马替尼血药浓度对临床个体化治疗的指导意义。方法对全国6家综合性医院入组的416例CML患者进行伊马替尼治疗后血浆谷浓度检测，评价伊马替尼血浆谷浓度与患者年龄、体重、体表面积的相关性以及与剂量、疗效的关系。结果①伊马替尼血浆谷浓度与患者年龄、体重和体表面积均无明显相关性。②中位伊马替尼血浆谷浓度为1271（109～4329）μg／L。伊马替尼血浆谷浓度与伊马替尼服用剂量有关，服用剂量〈400mg／d、400mg／d和〉400mg／d组在伊马替尼血浆谷浓度分别为（969±585）、（1341±595）和（1740±748）μg／L（P〈0．01）。⑧获得完全细胞遗传学反应（CCyR）与未获得CCyR患者伊马替尼血浆谷浓度分别为（1337±571）μg／L和（1354±689）μg／L，差异无统计学意义（P=0．255）。④伊马替尼血浆谷浓度对部分患者治疗具有指导意义。结论我国CML患者服用伊马替尼后血药浓度的个体差异大；伊马替尼血浆谷浓度与其获得CCyR之间无明显相关性；增加伊马替尼剂量能提高伊马替尼血浆谷浓度，对于部分患者的治疗有一定的指导意义。

Objective To evaluate the relationship between plasma trough level of imatinib and clinical outcomes in Chinese CML patients. Methods Plasma trough levels in 416 CML patients who received imatinib orally in six general hospitals were assessed. The correlations of imatinib plasma trough level with baseline characteristics including age, weight and BSA, and clinical response were evaluated. Results （1） Effects of age, body weight and BSA on imatinib plasma trough levels were not to be clinically significant. （2） Median imatinib plasma trough levels was 1271 （ 109 - 4329 ）. Imatinib plasma trough level was related to dose of imatinib administration. Plasma trough levels at imatinib of dose 〈 400, 400 and 〉 400 mg were （969 ±585 ）, （ 1341 ±595 ） and （ 1740 ±748 ） μg/L （ P 〈 0.01 ）, respectively. （3）There was no statistic diffence in imatinib plasma trough level with complete cytogenetic response [ CCyR（ 1337 ±571 ）μg/L vs no CCyR（ 1354 ±689 ）μg/L, P = 0. 2551- （4）Imatinib plasma trough level might be important for a good clinical response in some CML patients. Conclusion There was a large interpatient variability in imatinib plasma concentration in Chinese CML patients. No correlation of imatinib plasma trough level with CCyR was observed. However, higher doses of imatinib were shown to attain greater trough plasma concentration, suggesting that imatinib plasma trough level might be important for a good clinical response in some CML patients.