Population pharmacokinetic and pharmacogenetics of imatinib in Chinese patients with chronic myeloid leukemia

被引：9

作者：

Wang, Qing ^{[1
,2
]}

Jiang, Zhi-Ping ^{[3
]}

Yu, Er-Qian ^{[4
,5
]}

Zeng, Jing ^{[6
]}

Zhu, Yan ^{[1
,2
]}

Cai, Hua-Lin ^{[1
,2
]}

Yan, Miao ^{[1
,2
]}

Xiang, Da-Xiong ^{[1
,2
]}

Zhao, Xie-Lan ^{[3
]}

Xu, Ping ^{[1
,2
]}

Jiao, Zheng ^{[4
]}

Hoan Linh ^{[1
,2
,7
]}

机构：

[1] Cent S Univ, Xiangya Hosp 2, Dept Pharm, Changsha 410011, Hunan, Peoples R China

[2] Cent S Univ, Inst Clin Pharm, Changsha 410011, Hunan, Peoples R China

[3] Cent S Univ, Xiangya Hosp, Dept Hematol, Lab Clin Pharmacol, Changsha 410008, Hunan, Peoples R China

[4] Fudan Univ, Huashan Hosp, Dept Pharm, Shanghai 200040, Peoples R China

[5] Wenzhou Med Univ, Affiliated Hosp 1, Wenzhou 325000, Zhejiang, Peoples R China

[6] Li Huili Eastern Hosp, Ningbo Med Ctr, Dept Educ & Res, Ningbo 315000, Zhejiang, Peoples R China

[7] Univ Alberta, Dept Family Med, Fac Med & Dent, 6-10 Univ Terrace, Edmonton, AB T6G 2T4, Canada

来源：

PHARMACOGENOMICS | 2019年 / 20卷 / 04期

关键词：

chronic myeloid leukemia; imatinib; polymorphisms; population pharmacokinetics; transporter; TROUGH CONCENTRATION; POLYMORPHISMS; DASATINIB; NILOTINIB;

D O I：

10.2217/pgs-2018-0139

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Aim: This study aimed to establish a population pharmacokinetic (PPK) model in Chinese patients with chronic myeloid leukemia, and to quantify the effects of pharmacogenetics on pharmacokinetic parameters of imatinib. Methods: A total of 229 plasma concentrations from 170 patients were analyzed. Nonlinear mixed effect model was used to establish the PPK model. Results: A one-compartment model with first-order absorption and first-order elimination adequately describes imatinib pharmacokinetics. Actual bodyweight shows slight effect on the estimated apparent clearance (CL/F) of imatinib in this study population. The final PPK model is: K-a (1/h)=0.329; CL/F (l/h)=9.25x(actual bodyweight/70)(0.228); V/F(l)=222. Conclusion: Actual bodyweight has a slight effect on CL/F. Demographics, physiopathology and pharmacogenetics covariates have no significant effects on imatinib pharmacokinetics.

引用

页码：251 / 260

页数：10

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