伊马替尼现在是治疗慢性髓性白血病的一线选择药物。然而，对于中国患者的现实世界数据有限，无法支持个体化医学。本研究旨在描述中国慢性髓性白血病患者的人群药动学，研究一些协变量对伊马替尼暴露的影响，并为个体化医学和剂量减少提供支持。共招募了230名慢性髓性白血病患者，进行了424次稳态浓度测量，以进行人群药动学分析和菲尼克斯NLME软件的蒙特卡洛模拟。评估了人口统计学、生物学和药物基因组学（与CYP3A4、CYP3A5、ABCB1、ABCG2、SCL22A1和POR相对应的10个SNP）协变量对清除率的影响。一室模型最佳描述了伊马替尼的药代动力学。血红蛋白和估算的肾小球滤过率（<85 mL⋅min-1⋅1.73 m2）与伊马替尼的清除率相关。与药动学相关的遗传多态性对伊马替尼的清除率没有显著影响。最终模型的参数估计值为：ka（h-1）= 0.329，Vd/F（L）= 270，CL/F（L⋅h-1）= 7.60。在研究人群中，血红蛋白和估算的肾小球滤过率是解释伊马替尼暴露变异性的重要协变量。在治疗中，对于伴有中度至重度肾功能损害和显著血红蛋白变化的患者需要谨慎对待。© 2023年，作者独家授权给Springer-Verlag GmbH Germany，Springer Nature的一部分。

Imatinib is presently the first-line choice for the treatment of chronic myeloid leukemia. However, there are limited real-world data on Chinese patients to support individualized medicine. This work aims to characterize population pharmacokinetics in Chinese patients with chronic myeloid leukemia, investigate the effects of several covariates on imatinib exposure, and provide support for personalized medicine and dose reduction.A total of 230 patients with chronic myeloid leukemia were enrolled, and 424 steady-state concentration measurements were taken to perform the population pharmacokinetic analysis and Monte Carlo simulations with Phoenix NLME software. The effects of the demographic, biological, and pharmacogenetic (ten SNP corresponding to CYP3A4, CYP3A5, ABCB1, ABCG2, SCL22A1 and POR) covariates on clearance were evaluated.A one-compartmental model best-described imatinib pharmacokinetics. The hemoglobin and the estimated glomerular filtration rate (< 85 mL⋅min-1⋅1.73 m2) were associated with imatinib clearance. The genetic polymorphisms related to pharmacokinetics were not found to have a significant effect on the clearance of imatinib. The final model estimates of parameters are: ka (h-1) = 0.329; Vd/F (L) = 270; CL/F (L⋅h-1) = 7.60.Key covariates in the study population accounting for variability in imatinib exposure are hemoglobin and the estimated glomerular filtration rate. There is some need for caution when treating patients with moderate-to-severe renal impairment and significant hemoglobin changes.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.