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目的探讨大剂量甲氨蝶呤(HDMTX)在儿童急性淋巴细胞白血病(ALL)治疗中各时间点的血药浓度与患儿病理生理状态的关系,发现影响药物体内消除因素,为甲氨蝶呤群体药动学研究提供线索,为临床治疗提供依据。方法89例ALL患儿接受HDMTX化疗,观察内容包括患儿性别、年龄(按月)、体重、身高、体表面积、单位体表面积MTX用量、血药浓度、化疗前肝、肾功能、单位体表面积液体出量、对应PH等逐一进行对比,分析各因素对MTX消除影响。结果高剂量组在24h、36h、42h、48h时药物浓度显著高于低剂量组(P<0.05);体型偏瘦患儿药物体内消除明显快于体型偏胖者(P<0.05);单位体表面积液体出量高的患儿MTX排泄相对快,表现在42h,48h,72h,96h药物浓度明显低(P<0.05),统计48h药物浓度大于1.2μmol/L事件:低出量组33例,高出量组21例,有统计学差异(χ2=4.39)。液体排出量明显影响药物体内消除;血清蛋白偏高组24h、36h、48h、72h、96h血药浓度低于蛋白偏低组,在24h、36h、48h有统计学意义(P<0.05);患儿性别、年龄与血药浓度无相关性,不影响药物在体内的消除。结论甲氨蝶呤量、患儿体型、液体出量、肝功等明显影响MTX体内消除。
Objective To investigate the relationship between the plasma concentration of high-dose methotrexate (HDMTX) in children with acute lymphoblastic leukemia (ALL) at various time points and the pathophysiological status of children, and to find out the factors that influence the elimination of drugs in vivo. Methotrexate Collective pharmacokinetic studies provide clues, to provide the basis for clinical treatment. Methods Eighty-nine children with ALL underwent HDMTX chemotherapy. The observation included sex, age (monthly), body weight, height, body surface area, MTX per unit body surface area, blood concentration, liver and kidney function before chemotherapy, body surface area Liquid volume, the corresponding PH one by one compared to analyze the impact of various factors on the elimination of MTX. Results The drug concentration in high-dose group was significantly higher than that in low-dose group at 24h, 36h, 42h and 48h (P <0.05) MTX excretion was relatively fast in children with high surface area fluid output, which was significantly lower at 42h, 48h, 72h and 96h (P <0.05). Statistics 48h drug concentration was greater than 1.2μmol / L. Higher than the volume group of 21 cases, there was a statistically significant difference (χ2 = 4.39). Liquid excretion significantly affected the elimination of drugs in vivo; serum protein in high group 24h, 36h, 48h, 72h, 96h plasma concentration lower than the protein low group, at 24h, 36h, 48h statistically significant Children sex, age and plasma concentration without correlation, does not affect the elimination of drugs in the body. Conclusion Methotrexate, body size, fluid output and liver function obviously affect the elimination of MTX in vivo.