大剂量甲氨蝶呤在急性淋巴细胞白血病患儿体内的药动学研究  

Pharmacokinetics of High-Dose Methotrexate Infusion in Children with Acute Lymphoblastic Leukemia

作　　者：张善堂[1] 屈建[1] 杨林海[2] 唐丽琴[1] 王宁玲[2] 

机构地区：[1]安徽医科大学附属省立医院,安徽省立医院药剂科,合肥230001 [2]安徽医科大学附属省立医院,安徽省立医院儿科,合肥230001

出　　处：《中国现代应用药学》2008年第5期454-458,共5页Chinese Journal of Modern Applied Pharmacy

摘　　要：目的研究急性淋巴细胞白血病(ALL)患儿接受大剂量甲氨蝶呤(HDMTX)静脉滴注联合甲酰四氢叶酸钙解救方案治疗时甲氨蝶呤的药动学。方法采用高效液相色谱法测定16例ALL患儿使用甲氨蝶呤后不同时间点血清药物浓度,所得血药浓度-时间数据经DAS软件拟合,优化药动学房室模型,计算其药动学参数。结果大剂量甲氨蝶呤在急性淋巴细胞白血病患儿体内的经时过程符合二房室模型,主要药动学参数分别为:t1/2α=(1.61±0.43)h,t1/2β=(11.05±3.54)h,V1=(18.552±5.902)L·m-2,Cl=(4.525±1.181)L.h-1.m-2,k10=(0.254±0.053)h-1,k12=(0.194±0.043)h-1,k21=(0.074±0.025)h-1,AUC(0-t)=(1064.0±258.6)μmol.h.L-1,AUC(0-∞)=(1433.6±485.2)μmol·h·L-1,tmax=24h,Cmax=(40.1±10.3)μmol·L-1。结论大剂量甲氨蝶呤在急性淋巴细胞白血病患儿体内的药动学符合二房室模型,主要药动学参数有较明显的个体差异。OBJECTIVE To evaluate the pharmacokineties of methotrexate（MTX） in children with acute lyrnphoblastic leukemia （ALL） treated with high-dosage infusion of MTX and combination with calcium folinate （CF） rescued. METHODS The serum samples were collected at different time points in 16 ALL children after infusion of MTX. MTX concentrations in serum were detected by HPLC and DAS2.0 software was used to analyze the pharmacokinetics parameters. RESULTS The time-concentration course of HDMTX in ALL children were fitted to two-compartment model and the main pharmacokinetics parameters were as follow： t1/2α = （ 1.61 ±0.43）h,t1/2β= （11.05±3.54）h,V1 =（18.552±5.902）L·m^-2,Cl=（4.525±1.181）L·h^-1·m^-2,k10=（0.254±0.053） h^-1, k12 = （0.194 ± 0.043 ） h^-1, k21 = （ 0. 074 ± 0. 025 ） h^-1, AUC（0-4） = （ 1064.0 ± 258.6 ） μmol·h·L^-1, AUC（0-∞ ） = （ 1433.6 ± 485.2） μmol·h·L^-1 ,tmax = 24 h, Cmax = （ 40.1 ± 10.3 ） μmol·L^-1. CONCLUSION The pharmacokinetic process of HDMTX in ALL children were fitted to two-compartment model and the main pharmacokinetics parameters had individual difference.

关 键 词：甲氨蝶呤 急性淋巴细胞白血病 儿童 药动学 高效液相色谱法 

分 类 号：R969.1[医药卫生—药理学] R979.12[医药卫生—药学]