中国实用儿科杂志2011，Vol.26Issue(2)：104-107,4.
淋巴系恶性肿瘤患儿5g/m2氨甲蝶呤的群体药动学研究
Population pharmacokinetics of high-dose methotrexate in childhood lymphoid malignancies
刘玲 1华瑛 1赵卫红 1卢新天 1马岳红 1卢薇薇 1杜军保 1卢炜2
作者信息
- 1. 北京大学第一医院儿科,北京,100034
- 2. 北京大学医学部药学院,北京,100191
- 折叠
摘要
Abstract
Objective To establish the population pharmacokinetic model of high-dose methotrexate (HDMTX)5 g/m2 in children with lymphoid malignancies, and evaluate characteristics of pharmacokinetic parameters about the elimination delay of HDMTX 5 g/m2.Maethods Fifty-one children with lymphoid malignancies received 194 courses of HDMTX 5 g/m2.Measure MTX in plasma by FPIA.An extended least squares approach to nonlinear mixed effects modeling (NONMEM) was used to estimate pharmacokinetic parameters, intersubject and residual variability.Explain this variability in terms of patient specific information such as age or body weight and so on.Evaluate characteristics of pharmacokinetic parameters about the elimination delay of HDMTX 5g/m2.Results The following population parameters were obtained using a two-compartment open model.Clearance of central compartment (CL1)= 5.61 × (1 - 0.0183 ×(Age-8.3) + 0.00683 × (WBC-7.12) ) L/(h· m2), inter-compartment clearance (CL2) = 0.239 L/(h· m2), central volume (V1)= 12.1 × (1 +0.0369 × (BUN-3.52))L/m2,perilpheral volume(V2)=2.83 × (1 +0.00102 × (PLT-254.6))L/m2.The constant of distribution phase was α , the average being 0.469/h, ranging from 0.14/h to 1.96/h.The constant of elimination phase was β , the average being 1.645/h, ranging from 0.02/h to 0.3/h.The elimination phase started 7 distribution phases later.Both the inter-compartment clearance and the peripheralvolume of the elimination delay group were clearly larger than that of the non-elimination delayone.Conclusions The WBC of patient may have influence on the cleaance of central compartment BUN on the central volume and the PLT on the peripheral volume.There might be more MTX distributing to the peripheral volume, if elimination delay happened.As a result of rescue based on the measurement of MTX concentration in plasma, the toxicity effect of elimination delay group could be controlled.关键词
儿童/淋巴系恶性肿瘤/大剂量氨甲蝶呤/群体药动学分类
医药卫生引用本文复制引用
刘玲,华瑛,赵卫红,卢新天,马岳红,卢薇薇,杜军保,卢炜..淋巴系恶性肿瘤患儿5g/m2氨甲蝶呤的群体药动学研究[J].中国实用儿科杂志,2011,26(2):104-107,4.
