大剂量甲氨蝶呤血药浓度监测与影响因素分析

目的研究采用大剂量甲氨蝶呤（MTX）化疗的急性淋巴细胞白血病（ALL）患者MTX血药浓度的影响因素。方法采用高效液相色谱法测定MTX给药后24h、48h、72h血药浓度，实时荧光定量PCR法分析ABCC24240C〉T和4568A〉C基因型，多重线性回归逐步筛选变量法分析血药浓度与年龄、基因型等因素的关系。结果MTX给药剂量、基因型（ABCC24240C〉T和4568A〉C）~够影响MTX48h和72h血药浓度，MTX用药次数与MTX的48h浓度成正比。结论MTX血药浓度监测与ABCC24240C〉T和4568A〉C基因型检测对MTX的个体化用药具有指导意义。

Serum Concentration in High-dose Methotrexate Treatment and Related Factors

Objective To investigate the factors influencing the methotexate（MTX） concentration in acute lymphoblasdc leukemia patients. Methods The serum concentration of MTX at 24h, 48h and 72h was determined by HPLC. The genotype of ABCC2 4240C 〉T and 4568A〉C was analyzed by real-time qPCR. Multi-linear regression with stepwise was conducted to select the factors that affected MTX concentration. Results MTX dose, ABCC2 4240C〉T and 4568A〉C were able to affect the MTX concentration at 48h and 72h. MTX treatment duration was related to the increased MTX concentration at 481-L Conclusion Clinical monitoring of MTX concentration as well as detecting ABCC2 4240C〉T and 4568A〉C genotype could reduce the occurrence of adverse reaction.