中国胃肠间质瘤患者服用伊马替尼稳态谷浓度的初步分析

目的：研究中国胃肠间质瘤（gastrointestinal stromal tumor，GIST）患者服用伊马替尼稳态浓度的分布情况，为开展伊马替尼治疗药物浓度监测和个体化治疗提供依据。方法：收集服用甲磺酸伊马替尼达稳态（29 d）的GIST患者血浆，HPLC-MS/MS法检测血浆伊马替尼浓度。分析不同剂量伊马替尼血药浓度的差异以及个体间和个体内变异。结果：共收集88例GIST患者的154份血浆样本。服用伊马替尼600 mg·d^-1（n=4）、400 mg·d^-1（n=81）、300 mg·d^-1（n=1）、200 mg·d^-1（n=2）的患者血药浓度分别为（3 032.50±679.94）ng·mL^-1，（1 525.14±599.87）ng·mL^-1，1 155 ng·mL^-1，（655.57±21.92）ng·mL^-1。伊马替尼个体间变异39.57%，个体内变异为22.32%。单变量分析显示，伊马替尼血药浓度与性别、年龄、肿瘤切除部位以及是否转移无关。结论：中国GIST患者服用伊马替尼血药浓度个体差异较大，十分有必要进行血药浓度监测。

Distribution of imatinib trough concentration at steady state in Chinese patients with gastrointestinal stromal tumor

OBJECTIVE To evaluate the distribution of imatinib trough concentration at steady state (C_min) in Chinese patients with gastrointestinal stromal tumor (GIST), and provide a basis for therapeutic drug monitoring and individualized therapy of imatinib.METHODS Plasma samples were collected from a subset of patients with imatinib level at steady-state (SS, day 29). Imatinib plasma levels were analyzed using HPLC-MS/MS method. Imatinib concentrations at different doses were evaluated, and inter-patient and intra-patient variations were also calculated.RESULTS A total of 154 plasma samples were collected from 88 GIST patients. In patients treated with imatinib 600 mg·d^-1 (n=4), 400 mg·d^-1 (n=81), 300 mg·d^-1 (n=1) and 200 mg·d^-1 (n=2), imatinib C_min values were (3 032.50±679.94)ng·mL^-1, (1 525.14±599.87)ng·mL^-1, 1 155 ng·mL^-1 and (655.57±21.92)ng·mL^-1, respectively. The mean inter- and intra-patient variation rates were 39.57% and 22.32%, respectively. In univariate analyses, imatinib C_min was not correlated with sex, age, tumor resection site or metastasis.CONCLUSION It is necessary to implement therapeutic drug monitoring of imatinib in clinical routines due to the large inter-patient variation in Chinese GIST patients.