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。
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.
出处
《肿瘤防治研究》
CAS
CSCD
北大核心
2015年第11期1148-1151,共4页
Cancer Research on Prevention and Treatment
关键词
甲氨蝶呤
联合用药
急性肾损伤
血药浓度
Methotrexate(MTX)
Drug combination
Acute kidney injury(AKI)
Blood concentration