大剂量甲氨蝶呤治疗急性淋巴细胞白血病的血药浓度监测

目的研究大剂量甲氨蝶呤（HD—MTX）治疗急性淋巴细胞白血病（ALL）的药代动力学，血、脑脊液MTX浓度与不良反应以及指导四氢叶酸钙（CF）的解救。方法ALL患儿20例共接受36例次MTX3g·m^-2·次^-1治疗，采用高效液相色谱法（HPLC）检测患儿血清、脑脊液MTX浓度，并记录不良反应，同时根据血药浓度指导CF解救。结果不同个体及同一个体不同时问使用同一种给药方案的血药浓度、脑脊液浓度个体差异大；44h、68h与23h血药浓度的相关性无显著性，而44h与68h血药浓度的相关性有显著性（P〈0．01）；与低危组比较，中高危组采用3g·m^-2·次^-1剂量不能达到有效血药浓度（P〈0．01）。结论低危患儿采用3g·m^-2·次^-1是合理的，经合理水化碱化等保护性治疗措施后无严重不良反应发生，而对中高危患儿，需采用5g·m^-2·次^-1剂量。

Monitoring of Serum Concentration of High-dose Methotrexate in Treating Acute Lymphoblastic Leukemia

Objective To study the pharmacokinetics of high-dose methotrexate（HD-MTX）, and serum and cerebrospinal fluid （CSF） concentration of MTX and toxicity effect in treating acute lymphoblastic leukemia（ALL）,and to define leucovorin（CF） rescue protocol. Methods 20 cases of children with ALL received the treatment with HD-MTX of 3 g/m^2 for 36 courses. MTX serum and CSF concentration were measured by HPLC. And toxicity effects were registered. And CF dose was adjusted according to MTX serum concentration. Results Large individual differences of MTX concentration in serum and CSF were exhibited in different individuals and even in the same patient at different administering time. The serum concentration at 44 h,68 h have no correlaton with those at 23h, and 44 h have positive correlation with 68 h（P〈0. 01）. In compared to low-risk group, mid-risk and high-risk group can not reach the the effective serum concentration by using MTX 3 g/m^2（P〈0. 0l）. Conclusion For low-risk ALL children, the administration of a dose of 3 g/m^2 was reasonable. And no severe adverse effects were occurred according to reasonable hydration and alkalization. Mid-risk and high-risk ALL children need a dose of 5 g/m^2,respectively.