国产伊马替尼治疗慢性髓性白血病的血药浓度与疗效分析

Analysis of correlation between plasma trough level and response of generic imatinib in the treatment of Chinese patients with chronic myeloid leukemia

目的评价我国慢性髓性白血病慢性期(CML-CP)患者接受国产伊马替尼(商品名:格尼可)治疗后伊马替尼及其代谢物血浆谷浓度水平与疗效的关系。方法以2012年10月11日至2013年5月8日入组编号为YMTN1.0临床研究的21例接受国产伊马替尼治疗的CML-CP患者为研究对象,评价其血浆药物谷浓度与疗效、年龄、体重、体表面积的关系。伊马替尼及其代谢物浓度检测采用高效液相色谱-串联质谱法。结果①伊马替尼及其代谢物血浆谷浓度分别为(1185.07±417.91)μg/L和(251.53±76.50)μg/L。②伊马替尼及其代谢物血浆谷浓度与患者年龄、体重和体表面积均无明显相关性(P值均>0.05)。③伊马替尼稳态血浆谷浓度高于1000μg/L的患者其完全及主要分子学反应率显著高于未达1000μg/L的患者(42%对0,P<0.01)。结论接受国产伊马替尼治疗的CML-CP患者中,伊马替尼及其代谢产物稳态血浆谷浓度存在较大个体差异,伊马替尼血浆谷浓度与患者获得分子学疗效有一定的相关性。

Objective To analyze the correlation between plasma trough level of generic imatinib and its metabolism and clinical outcomes in Chinese patients with chronic myeloid leukemia in chronic phase(CML-CP).Methods The 21 patients with CML-CP who enrolled in a clinical trial YMTN 1.0 from Oct 11th,2012 to May 8th,2013 and received generic imatinib were as study subjects.The correlation between steady plasma trough levels of imatinib and its metabolism with clinical response,age,weight and body surface area(BSA)were evaluated.Results①The mean steady plasma trough level of generic imatinib and its metabolism was(1185.07±417.91)μg/L and(251.53±76.50)μg/L,respectively.②Age,weight and BSA has no significant effects on plasma trough level of generic imatinib and its metabolism(P>0.05).③Patients with steady plasma trough level of generic imatinib more than 1000μg/L are possible to have higher major molecular response(MMR)/complete molecular response(CMR)rate than those below 1000μg/L(42%vs 0,P<0.05).Conclusion Plasma trough levels of generic imatinib varied in CML patients.The steady plasma trough levels of generic imatinib is maybe related to molecular response in CML patients.