血药浓度监测在大剂量甲氨蝶呤治疗中的应用价值

目的 探讨血药浓度监测在大剂量甲氨蝶呤(MTX)治疗血液系统肿瘤中的应用价值.方法 给予105例急性淋巴细胞白血病及淋巴瘤患者217例次大剂量MTX(1.5～9.0 g)治疗,根据MTX的血药浓度,以不同剂量及不同给药方式给予四氢叶酸钙(CF)解救.于开始用药44h起,间隔6～12h用荧光偏振免疫法测定MTX血药浓度,监测至MTX浓度<0.1 μmol/L止.结果 6例次(2.8%)患者开始用药44h后MTX浓度(C_(MTX/44h))≥5 μmol/L,平均浓度为11.67μmol/L(6.01～20.15 μmol/L),平均解救中止时间为开始用药170 h(92～272 h);23例次(10.6%)患者1 μmol/L≤C_(MTX/44h)<5μmol/L,平均浓度为2.23 μmol/L(1.07～4.69 μmol/L),平均解救中止时间为开始用药116 h(68～188 h)后.C_(MTX/44h)≥1 μmol/L者基本出现于使用MTX剂量≥5 g的患者中.除个别患者出现轻度黏膜炎症外,所有患者均未发生严重不良发应.结论 MTX的代谢过程存在个体差异,应进行血药浓度监测.排泄延迟更易出现于使用高剂量药物时.在血药浓度监测下使用大剂量MTX安全可行.

Blood Concentration Monitoring during High-dose Methotrexate Treatment

Objective To explore the clinical value of blood concentration monitoring during high-dose methotrexate (MTX) treatment Methods High-dose MTX (1.5-9.0 g) was infused to 105 patients with acute lymphoblastic leukemia or lymphoma, and then the blood MTX concentration was measured by fluorescence polarization immune assay (FPIA) 44 hours after the start of administration. The procedure was repeated every 6-12 hours until the concentration was less than 0. 1 μmol/L Results Forty-four hours after the start of administration, the blood MTX concentration (C_(MTX/44h)) was ^5 μmol/L in 6 patients (2. 8%) and was between 1 and 5 μmol/L in 23 patients (10. 6%). C_(MTX/44h) ≥ 1 μmol/L was more common in patients received 5. 0 g MTX. No severe adverse event was observed in all patients. Conclusions Blood MTX concentration is different after high-dose MTX treatment due to individual metabolic differences, and therefore it is clinically important to monitor blood concentration of MTX. Elimination delay is more common in patients receive 5. 0 g MTX. Application of high-dose MTX therapy under the monitoring of blood MTX concentration is safe and feasible.