大剂量甲氨蝶呤在成人非霍奇金淋巴瘤患者中的群体药动学研究  

Population pharmacokinetics study of high-dose methotrexate in adult patients with non-Hodgkin lymphoma

作　　者：黎顺发 王宇[2] 殷李娟 詹靖[2] 冯崑尧 李苏[2] 张建萍[1] LI Shunfa;WANG Yu;YIN Lijuan;ZHAN Jing;FENG Kunyao;LI Su;ZHANG Jianping(College of Pharmacy,Ji’nan University,Guangzhou 510632,China;Sun Yat-Sen University Cancer Center,Guangzhou 510060,China)

机构地区：[1]暨南大学药学院,广州510632 [2]中山大学肿瘤防治中心,广州510060

出　　处：《中国临床药学杂志》2022年第5期339-345,共7页Chinese Journal of Clinical Pharmacy

摘　　要：目的建立大剂量甲氨蝶呤(HD-MTX)在成人非霍奇金淋巴瘤(NHL)患者中的群体药动学模型,探讨影响甲氨蝶呤消除和分布的因素,以期为患者个体化用药提供参考。方法收集使用HD-MTX的NHL患者(年龄>18岁)的临床资料,包括药动学资料以及人口统计学资料,在Monolix软件(版本2019R2)中使用非线性混合效应模型法建立群体药动学模型。结果二室模型能够较好地拟合数据,最终模型:中央室清除率(CL)=11.1×(年龄/46)^(-0.24)×(体表面积/1.67)^(0.796)×(胱抑素C/0.84)^(-0.342)L·h^(-1);中央室分布容积(V_(1))=23.8×(体质量/60)^(0.698)L;室间清除率(Q)=0.544 L·h^(-1);外周室分布容积(V_(2))=4.96 L。验证结果表明,最终模型具有良好的稳定性和预测性能。结论本研究建立的针对成人NHL患者的HD-MTX群体药动学模型,能够较好地描述数据特征,具有良好的稳定性和预测性能,能为临床上个体化给药提供一定的参考.AIM To establish a population pharmacokinetic model of high-dose methotrexate(HD-MTX)in adult patients with non-Hodgkin lymphoma(NHL),and to explore the factors affecting the elimination and distribution of methotrexate,in order to provide a reference for patients'individualized medication.METHODS The pharmacokinetic and demographic data of NHL patients(>18 years old)treated with HD-MTX were collected,and the nonlinear mixed-effects model in the Monolix software(version 2019R2)was used to establish a population pharmacokinetic model.RESULTS The two-compartment model fitted the data well,and the formula of the final model was CL=11.1×(AGE/46)^(-0.24)×(BSA/1.67)^(0.796)×(CYSC/0.84)^(-0.342)L·h^(-1);V_(1)=23.8×(WT/60)^(0.698)L;Q=0.544 L·h^(-1);V_(2)=4.96 L.The verification results showed that the final model had good stability and predictive performance.CONCLUSION The population pharmacokinetic model of HD-MTX established in the study for adult NHL patients can describe the data characteristics well and has good stability and predictive performance.It can be useful for providing some references for individualized drug administration in clinical practice.

关 键 词：大剂量甲氨蝶呤 非霍奇金淋巴瘤 群体药动学 非线性混合效应模型法 

分 类 号：R733.1[医药卫生—肿瘤]