急性淋巴细胞白血病治疗中大剂量甲氨蝶呤血药浓度影响因素分析

High-dose methortrexate therapy in children with acute lymphoblastic leukemia in blood concentration analysis

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 Study of high-dose methotrexate （HDMTX） in the treatment of children with acute lymphoblastic leukemia （ALL） in the time of the blood concentration of children with physiological and pathological state of the relationship, to provide basis for clinical treatment, find effects of the drug in the body to eliminate factors, provides clues of Methotrexate for the child population pharmacokinetics study. Methods 89 cases of ALL children undergoing HD-MTX chemotherapy, records of the children, including sex, age （monthly）, weight, height, body surface area, body surface area unit volume MTX, serum electrolytes,liver and kidney function before chemotherapy, unit volume of a liquid body surface area, the corresponding pH by comparison, the analysis of the factors on the impact of the elimination of MTX. Results Methotrexate, size of children, volume of liquid, PH value, liver function, have significant effect on the body to eliminate MTX, clinical and drug use prompted MTX groups Pharmaeokinetics.