东北地区小儿急淋白血病大剂量甲氨蝶呤化疗后血药浓度与不良反应相关性分析  

Associability of adverse drug reactions and blood drug concentration in acute lymphoblastic leukemia children in north-east area received high dose of methotrexate chemotherapy

作　　者：何晓静[1] 邱枫[1] 肇丽梅[1] 孙亚欣[1] 朱旭[1] 

机构地区：[1]中国医科大学附属盛京医院药学部,辽宁沈阳110004

出　　处：《中国现代医学杂志》2010年第5期718-722,共5页China Journal of Modern Medicine

基　　金：国家自然科学基金面上项目(No:30973597)

摘　　要：目的研究东北地区小儿急性淋巴细胞白血病大剂量甲氨蝶呤化疗时,甲氨蝶呤血药浓度的变化规律;分析甲氨蝶呤血药浓度与不良反应的相关性,制定合理的甲氨蝶呤解救方案;提供基础数据,为实现个体化给药奠定基础。方法搜集2007年1月～2009年7月在该院小儿血液内科接受甲氨蝶呤(3g/m2)化疗的东北地区小儿急性淋巴细胞白血病患者,并以此为研究对象。大剂量甲氨蝶呤化疗后,定时取血监测血药浓度,根据血药浓度结果制定救援方案。研究甲氨蝶呤血药浓度与不良反应的相关性,对结果进行安全性评价,制定合理的临床治疗方案。结果大剂量甲氨蝶呤化疗后48h不同个体血药浓度结果差异较大(0.10～23.00μmol/L);48h血药浓度大于1.0μmol/L的患者的解救次数和血药浓度监测次数均显著高于血药浓度小于1.0μmol/L(P<0.01);与血药浓度小于1.0μmol/L的病例比较,血药浓度大于1.0μmol/L的病例不良反应的病例有增加趋势,但统计结果不显著(P>0.05)。结论大剂量甲氨蝶呤化疗时,进行血药浓度监测可优化治疗方案。甲氨蝶呤的血药浓度升高有导致不良反应的增加的趋势,该不良反应可逆。临床治疗中,可根据病人情况将甲氨蝶呤剂量增至患儿可耐受剂量,定时监测并根据血药浓度结果制定解救方案,可最大程度降低不良反应的发生,提高治疗效果。【Objective】To study the clinical reference to determine individual remedy, the metabolic regularity of methotrexate （MTX） were studied and the associativity of drug adverse reactions and abnormal-blood drug concentration were analyzed. Finally, we could optimize the remedy and implement individualized drug administration. 【Methods】160 acute lymphoblastic leukemia children received HD-MTX （2.0～4.0 g/m） treatment were involved in this study. The serum samples were collected at different time after infusion started. The citrovorum factor rescue schema was determined with the result of MTX serum concentration in terminal elimination phase. The adverse reaction was also monitored to evaluate the remedy safety. 【Results】MTX concentration in serum had great imparity among individuals, especially with the serum concentration of terminal phase 48 h （0.10～23.00μmol/L）. The rescue and monitoring case of h-level group（1.0 μmol/L） was increased compared with the l-level group （1.0 μmol/L） （P 0.01）; The case of abnormal-liver function in h-level group has up tendency, but there were no statistical differences （P 0.05）. No long term survival data could be given. 【Conclusion】 It＇s necessary to determine individual remedy by serum concentration monitoring for adding MTX dosage to the extent that can be tolerated by all children. Abnormal blood methotrexate may result reversible abnormal liver function.

关 键 词：甲氨蝶呤 小儿急性淋巴细胞白血病 不良反应 血药浓度监测 

分 类 号：R733.7[医药卫生—肿瘤]