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.
[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
(8.0+极速模式)