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联合用药对大剂量甲氨蝶呤化疗治疗儿童急性淋巴细胞白血病肾毒性及血药浓度的影响

程道海, 陆华, 黄振光, 覃兴昆

程道海, 陆华, 黄振光, 覃兴昆. 联合用药对大剂量甲氨蝶呤化疗治疗儿童急性淋巴细胞白血病肾毒性及血药浓度的影响[J]. 肿瘤防治研究, 2015, 42(11): 1148-1151. DOI: 10.3971/j.issn.1000-8578.2015.11.020
引用本文: 程道海, 陆华, 黄振光, 覃兴昆. 联合用药对大剂量甲氨蝶呤化疗治疗儿童急性淋巴细胞白血病肾毒性及血药浓度的影响[J]. 肿瘤防治研究, 2015, 42(11): 1148-1151. DOI: 10.3971/j.issn.1000-8578.2015.11.020
CHENG Daohai, LU Hua, HUANG Zhenguang, QIN Xingkun. Influence of Drug Combinations on High-dose Methotrexate-induced Nephrotoxicity and Blood Concentrations of Childhood Acute Lymphoblastic Leukemia[J]. Cancer Research on Prevention and Treatment, 2015, 42(11): 1148-1151. DOI: 10.3971/j.issn.1000-8578.2015.11.020
Citation: CHENG Daohai, LU Hua, HUANG Zhenguang, QIN Xingkun. Influence of Drug Combinations on High-dose Methotrexate-induced Nephrotoxicity and Blood Concentrations of Childhood Acute Lymphoblastic Leukemia[J]. Cancer Research on Prevention and Treatment, 2015, 42(11): 1148-1151. DOI: 10.3971/j.issn.1000-8578.2015.11.020

联合用药对大剂量甲氨蝶呤化疗治疗儿童急性淋巴细胞白血病肾毒性及血药浓度的影响

详细信息
    作者简介:

    程道海(1981-),男,硕士,主管药师,主要从事临床药学工作

  • 中图分类号: R733.7; R730.53

Influence of Drug Combinations on High-dose Methotrexate-induced Nephrotoxicity and Blood Concentrations of Childhood Acute Lymphoblastic Leukemia

  • 摘要: 目的 探讨联合用药对大剂量甲氨蝶呤(MTX)化疗肾毒性及MTX血药浓度的影响。方法 采用回顾性分析方法,收集2012年9月至2014年9月广西医科大学第一附属医院178例儿童急性淋巴细胞白血病(ALL)患者共633例次大剂量MTX化疗的临床资料,根据化疗时用药情况分为两组,对照组为常规大剂量MTX化疗,联合用药组在此基础上联用了青霉素类、非甾体类抗炎药及质子泵抑制剂等,比较两组的急性肾损伤(AKI)发生率和MTX血药浓度。结果 有84例次大剂量MTX化疗时联合应用了哌拉西林、布洛芬和奥美拉唑等药物,联合用药组AKI总体发生率明显高于对照组(P<0.05),表现在中度和重度AKI发生率明显增加(P<0.05)。联合用药组各时间点MTX血药浓度明显高于对照组(P<0.05),MTX血药浓度降至安全范围所需天数明显长于对照组(P<0.05)。结论 大剂量甲氨蝶呤化疗时联用哌拉西林、布洛芬和奥美拉唑等药物会使MTX排泄延缓,肾毒性发生风险增加,应避免联用。

     

    Abstract: Objective To investigate the influence of drug combinations on high-dose methotrexate(MTX)- induced nephrotoxicity and MTX blood concentrations. Methods We retrospectively analyzed the clinical data of 178 childhood acute lymphoblastic leukemia(ALL) patients who received 633 courses of high-dose MTX therapies in the First Affiliated Hospital of Guangxi Medical University from Sep. 2009 to Sep. 2014. The patients were divided into two groups based on the medications taken: control group was treated with routine high-dose MTX, and the drug combination group was additionally given penicillins, non-steroidal anti-inflammatory drugs or proton pump inhibitors on the basis of control group. The incidences of acute kidney injury(AKI) and MTX blood concentrations were compared between two groups. Results The combinations of piperacillin, ibuprofen and omeprazole were observed in 84 courses of high-dose MTX therapies. The overall incidence of AKI in drug combination group was significantly higher than that in control group(P<0.05), which mainly manifested in a significantly increased incidences of moderate and severe AKI (P<0.05). MTX blood concentrations at each time point in drug combination group were significantly higher than those in control group(P<0.05). The days needed for MTX concentrations decreasing to the safe level in drug combination group were significantly longer than that in control group(P<0.05). Conclusion The combination of piperacillin, ibuprofen and omeprazole in high-dose MTX chemotherapy may lead to the excretion delay of MTX and increase the risk of renal toxicity. Such drug combinations should be avoided in the high-dose MTX therapies.

     

  • [1] Hematology Section of the Pediatrics Branch at the Chinese Medical Association, Editorial board of Chinese Journal of Pediatrics. Diagnosis and treatment of pediatric acute lymphoblastic leukemia (3rd revised)[J]. Zhonghua Er Ke Za Zhi, 20 06, 44(5): 392-5. [中华医学会儿科学分会血液学组,中华儿科 杂志编辑委员会. 儿童急性淋巴细胞白血病诊疗建议(第三次 修订草案) [J]. 中华儿科杂志, 2006, 44(5): 392-5.]
    [2] Ye H, Gu LJ, Chen J, et al. High dose methotrexate therapy in childhood acute lymphoblastic leukemia[J]. Zhonghua Xue Ye Xue Za Zhi, 2001, 22(7): 385-6. [叶辉, 顾龙君, 陈静, 等. 儿童急 性淋巴细胞白血病大剂量甲氨蝶呤治疗研究[J]. 中华血液学杂 志, 2001, 22(7): 385-6.]
    [3] Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. KDIGO clinical practice guideline for acute kidney injury[J]. Kidney Int, 2012, 2(1 Suppl): 1-138.
    [4] Pang L, Liu LM, Zhao LM. Research progress in influence factorsof excretion delay of high-dose methotrexate[J]. Zhongguo Yao Xue Za Zhi, 2013, 48(22): 1892-6. [庞露, 刘立民, 肇丽梅. 大剂 量甲氨蝶呤排泄延迟影响因素的研究进展[J]. 中国药学杂志, 20 13, 48(22): 1892-6.]
    [5] Takeda M, Khamdang S, Narikawa S, et al. Characterization of methotrexate transport and its drug interactions with human organic anion transporters[J]. J Pharmacol Exp Ther, 2002, 30 2(2): 666-71.
    [6] Zarychanski R, Wlodarczyk K, Ariano R, et al. Pharmacokinetic interaction between methotrexate and piperacillin/tazobactam resulting in prolonged toxic concentrations of methotrexate[J]. J Antimicrob Chemother, 2006, 58(1): 228-30.
    [7] El-Sheikh AA, van den Heuvel JJ, Koenderink JB, et al. Interaction of nonsteroidal anti-inflammatory drugs with multidrug resistance protein (MRP) 2/ABCC2- and MRP4/ABCC4-mediated methotrexate transport[J]. J Pharmacol Exp Ther, 2007, 320(1): 22 9-35.
    [8] Skeith KJ, Russell AS, Jamali F, et al. Lack of significant interaction between low dose methotrexate and ibuprofen or flurbiprofen in patients with arthritis[J]. J Rheumatol, 1990, 17(8): 1008-10.
    [9] Breedveld P, Zelcer N, Pluim D, et al. Mechanism of the pharmacokinetic interaction between methotrexate and benzimidazoles: potential role for breast cancer resistance protein in clinical drug-drug interactions[J]. Cancer Res, 2004, 64(16): 58 04-11.
    [10] Perazella MA. Crystal-induced acute renal failure[J]. Am J Med, 19 99, 106(4): 459-65.
    [11] Li D, Li XZ. Therapeutic effect of hemodialysis on acute kidney injury induced by high-dose methotrexate chemotherapy in children[J]. Shi Yong Er Ke Lin Chuang Za Zhi, 2012, 27(17): 13 20-2. [李迪, 李晓忠. 血液透析治疗大剂量甲氨蝶呤化疗 所致急性肾损伤的疗效[J]. 实用儿科临床杂志, 2012, 27(17): 13 20-2.]
    [12] Xu WQ, Tang YM, Fang CQ, et al. Study on elimination delay in high dose methotrexate therapy in childhood acute lymphoblastic leukemia[J]. Zhonghua Xue Ye Xue Za Zhi, 2005, 26(1): 15-8. [徐卫群, 汤永民, 方澄清, 等. 大剂量甲氨蝶呤治疗儿童急性淋 巴细胞白血病排泄延迟分析[J]. 中华血液学杂志, 2005, 26(1): 15 -8.]
    [13] Lu H, Zhong XB, Huang ZG, et al. Elimination delay of high-dose methotrexate in children with acute lymphoblastic leukemia[J]. Zhongguo Yao Fang, 2009, 20(29): 2265-8. [陆华, 钟小斌, 黄振 光, 等. 大剂量甲氨蝶呤治疗儿童急性淋巴细胞白血病排泄延 迟分析[J]. 中国药房, 2009, 20(29): 2265-8.]
    [14] Meng LY, Tian HP, Wang XJ, et al. The effect of MTHFR gene polymorphism in the toxic side effects of HD-MTX chemotherapy on children[J]. Er Ke Yao Xue Za Zhi, 2013, 19(2): 1-4. [孟琳懿, 田怀平, 王小洁, 等. 亚甲基四氢叶酸还原酶基因多态性对儿童 甲氨蝶呤化疗后毒副反应[J]. 儿科药学杂志, 2013, 19(2): 1-4.]
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出版历程
  • 收稿日期:  2014-11-16
  • 修回日期:  2015-01-03
  • 刊出日期:  2015-11-24

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