| 摘要: |
| 目的:探讨大剂量甲氨蝶呤(HDMTX)致严重排泄延迟及急性肾损伤(AKI) 的救治方案与药学监护。方法:1 例急性淋巴细胞白血病患儿,接受HDMTX 治疗后出现严重排泄延迟及3 期AKI。临床药师参与制定的阶梯式干预方案包括实施基于治疗药物监测(TDM)的个体化亚叶酸钙解救,强化水化、碱化以及在HDMTX 给药后54 h 启用连续性静脉-静脉血液透析滤过(CVVHDF)联合血液灌流(HP)。结果:干预后,MTX 血药浓度在116 h 降至1. 18 μmol/ L,236 h 降至安全阈值以下;肾功能显著改善并恢复至正常范围。药物基因组学分析提示MTHFR 677C>T 与ABCB1 3435C>T 杂合基因型,据此将后续HDMTX 剂量下调20%,患儿未再发生排泄延迟或AKI。结论:CVVHDF 联合HP 是清除HDMTX 的有效方法。建立覆盖风险评估、TDM 预警、阶梯式干预及个体化治疗的药学监护路径,对保障HDMTX 治疗安全具有重要意义。 |
| 关键词: 甲氨蝶呤 排泄延迟 急性肾损伤 亚叶酸钙 血液净化 |
| DOI：doi:10.13407/j.cnki.jpp.1672-108X.2026.04.005 |
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| 基金项目:福建省卫生健康计划项目青年研究课题,编号2023QNB013;厦门市自然科学基金项目,编号3502Z202372098;厦门市医疗卫生指导性项目,编号3502Z2024ZD1269。 |
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| Stepwise Intervention and Pharmaceutical Care for Severe Toxicity Induced by High-Dose Methotrexate |
| Lin Jinxiang, Wen Fengyun, Li Suping, Wang Jing, Zhang Qingchi, Xiao Zhifeng |
| ((Xiamen Children’ s Hospital (Children’s Hospital of Fudan University at Xiamen), Fujian Xiamen 361006, China)) |
| Abstract: |
| Objective: To explore the therapeutic regimen and pharmaceutical care for managing severe delayed excretion and acute kidney injury (AKI) induced by high-dose methotrexate (HDMTX). Methods: A pediatric patient with acute lymphoblastic leukemia developed severe delayed methotrexate excretion and stage 3 AKI after HDMTX administration. A stepwise intervention, developed with input from the clinical pharmacist, was implemented. The protocol comprised therapeutic drug monitoring (TDM)-guided individualized calcium folinate rescue, intensified hydration and urinary alkalinization, and initiation of continuous veno-venous hemodiafiltration (CVVHDF) combined with hemoperfusion (HP) at 54 h after HDMTX administration. Results: Following the interventions, the serum methotrexate concentration decreased to 1. 18 μmol/ L by 116 h and fell below the safety threshold by 236 h post-dose. Renal function progressively normalized by discharge. Pharmacogenomic analysis identified heterozygous MTHFR 677C > T and ABCB1 3435C > T genotypes. Based on these findings, the subsequent HDMTX dose was reduced by 20%, and the child experienced no further episodes of delayed excretion or AKI. Conclusion: CVVHDF combined with HP is effective for rapid methotrexate clearance. Establishing a pharmaceutical monitoring pathway that covers risk assessment, TDM warning, stepwise intervention, and individualized treatment is of great significance for ensuring the safety of HDMTX therapy. |
| Key words: methotrexate delayed excretion acute kidney injury calcium folinate blood purification |
