大剂量甲氨蝶呤治疗儿童白血病的药动学研究

Pharmacokinetics of high dose methotrexate in the treatment of pediatric lymphocytic leukemia

目的 研究 10例急性淋巴细胞白血病 (ALL)患儿应用大剂量甲氨蝶呤 甲酰四氢叶酸解救 (HDMTX CF疗法 )治疗的甲氨蝶呤 (MTX)药动学过程 ,确定联合用药下MTX的药动学参数 ,确定脑脊液浓度和外周血浓度的相关性。方法 用荧光偏振免疫 (FPIA)方法检测一定时间下的血清和脑脊液浓度。结果 MTX半衰期 (t1/2 )、表观分布容积 (Vd)、曲线下面积(AUC)、清除率 (CL)、平均滞留时间 (MRT)分别与 4 .10 ,4 1.0 7,2 4 7.83,6 .87,5 .72。 2h的脑脊液浓度和外周血浓度有正相关 (r =0 .76 )。结论 本研究为HDMTX CF疗法提供了客观有效的数据 。

OBJECTIVE: To study the pharmacokinetics of methotrexate (MTX) in children with acute lymphocytic leukemia (ALL) treated by high dosage of MTX and CF (HDMTX-CF), and the correlation between the concerntrations in C. S. F and serum. METHODS: The concerntrations of MTX in CSF and Serum were determined by FPIA. RESULTS: The pharmacokinetic parameters such as t1/2, Vd, AUC, CL and MRT were 4.10, 41.07, 247.83, 6.87 and 5.72 respectively. The correlation between the concerntrations of MTX in CSF and serum was positive (r = 0.76). CONCLUSION: The study provided useful data for HDMTX-CF treatment. And it confirmed the reliability and safety of the scheme.