大剂量甲氨蝶呤治疗骨肉瘤的血药浓度监测及其临床意义

目的监测大剂量甲氨蝶呤（high dose methotrexate，HD—MTX）治疗骨肉瘤患者的血药浓度，并探讨其临床意义。方法采用均相酶免疫分析法对接受HD—MTX化疗的10例骨肉瘤患者按照需要定时测定甲氨蝶呤（MTX）的浓度，分析各时间点MTX血药浓度特点及其与不良反应之间的关系。结果测得MTX0h平均浓度为（953．30±2350）μmol·L-1，72h平均浓度为（0．0860±0．0947）μmol·L-1，其中2例的72hMTX血药浓度大于中毒浓度，出现毒副反应，采用亚叶酸钙（cF）加大剂量、延长用药时间后，症状消失，所有患者均未发生严重不良发应。结论MTX各时间点的浓度存在个体差异，应进行血药浓度监测。在血药浓度监测下，及时调整CF的解救时间与剂量，使HD—MTX治疗安全可行。

Surveillance and the clinical significance of the plasma concentration of high-dosage methotrexate during chemotherapy for osteosarcoma

Objective To monitor and determine the plasma concentration of high - dosage methotrexate （ HD - MTX） during chemotherapy in patients with osteosarcoma and investigate its clinical significance. Methods Ten patients with osteosarcoma under chemotherapy with HD - MTX underwent determination of plasma MTX concentrations at an interval of 24 hours as required by homogeneous phase enzyme immunoassay to analyze the characteristics of serum MTX concentrations at each time point and the relationship between the serum MTX concentrations and the adverse reactions. Results The average concentration of MTX at 0 h was （953.30 ± 2 350） μmol·L-1 and the average plasma MTX concentration at 72 h was （0. 0860 ± 0. 0947 ） μmol·L-1. The plasma MTX concentration at 72 h was greater than toxic concentration in two patients, who displayed adverse reactions, which disappeared with increased dosage and pro- longed medication of calcium folinate （CF）. None of the patients had severe adverse reactions. Conclusion There is significant idiosyncratic variability in plasma MTX levels at each time point, and therefore it is clinically essential to monitor blood MTX concentration. With the surveillance of plasma MTX concentration, timely adjustment of rescue time and dosage of CF is the prerequisite to safe and feasible chemotherapeutic regimen with HD - MTX.