大剂量甲氨蝶呤治疗血液系统恶性肿瘤后排泄延迟的影响因素及其与不良反应的相关性研究

Influencing Factors of Delayed Excretion After High-Dose Methotrexate in Treatment of Hematological Malignant Tumor and its Correlation with Adverse Drug Reactions

目的:探讨血液系统恶性肿瘤患者采用大剂量甲氨蝶呤化疗方案后排泄延迟的影响因素及其与不良反应的相关性。方法:收集2016年7月至2018年6月常州市第一人民医院使用大剂量甲氨蝶呤并进行治疗药物监测的34例血液科恶性肿瘤患者共71次化疗疗程的临床资料及血药浓度数据,分析不同时间点影响甲氨蝶呤排泄的药物因素及患者因素,并考察排泄延迟与各系统不良反应的相关性。结果:开始给药后48、72 h时,甲氨蝶呤平均血药浓度分别为(1. 27±2. 49)、(0. 34±0. 48)μmol/L,排泄延迟率分别为25. 71%、30. 00%。排泄延迟患者开始给药后48、72 h时的甲氨蝶呤血药浓度明显高于正常排泄患者,差异均有统计学意义(P<0. 01);排泄延迟患者的甲氨蝶呤剂量、甲氨蝶呤体表面积剂量明显大于正常排泄患者,差异均有统计学意义(P<0. 05);与≤60岁患者比较,老年人(>60岁)在开始给药后72 h时更易出现排泄延迟(P=0. 003)。开始给药后48 h时排泄延迟者更易发生肝损伤(P=0. 027),但未见排泄延迟对其他系统不良反应的发生风险存在显著影响。结论:药物剂量和患者年龄对甲氨蝶呤排泄延迟有显著影响,排泄延迟者不良反应发生风险增加。

OBJECTIVE: To investigate the influencing factors of delayed excretion after high-dose methotrexate in chemotherapy of hematological malignant tumor and its correlation with adverse drug reactions. METHODS: Clinical data and blood concentration data were collected from 34 patients with hematological malignant tumor who received 71 high-dose methotrexate chemotherapy courses in the First People’s Hospital of Changzhou from Jul. 2016 to Jun. 2018.The influencing factors on MTX excretion at different time points were analysed,and the correlations between delayed excretion and adverse drug reactions in various systems were also investigated. RESULTS: At 48 h and 72 h after administration,the average blood concentration of methotrexate were respectively( 1. 27 ± 2. 49) μmol/L and( 0. 34±0. 48) μmol/L,with the excretion-delay rates were respectively 25. 71% and 30. 00%. The blood concentration of methotrexate in patients with delayed excretion at 48 h and 72 h after administration was significantly higher than that of patients with normal excretion,with statistically significant difference( P<0. 01);the dosage and body surface area dosage of methotrexate in patients with delayed excretion were significantly larger than those of patients with normal excretion,with statistically significant differences( P < 0. 05);compared with patients ≤ 60 years old,the elderly( >60 years old) were more prone to delay in excretion at 72 h after administration( P = 0. 003). Liver injury was more likely to occur in patients with delayed excretion at 48 h after administration( P = 0. 027),but no significant effect of delayed excretion on the risk of other systemic adverse drug reactions was observed. CONCLUSIONS: Drug dosage and patient’s age have significant effects on delayed excretion of methotrexate,and those with delayed excretion have an increasing risk of adverse drug reactions.