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

Pharmacogenomics. 2019 Mar;20(4):251-260. doi: 10.2217/pgs-2018-0139. Epub 2019 Feb 15.

Abstract

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: Ka (1/h) = 0.329; CL/F (l/h) = 9.25 × (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.

Keywords: chronic myeloid leukemia; imatinib; polymorphisms; population pharmacokinetics; transporter.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Variation, Population*
  • China / epidemiology
  • Female
  • Humans
  • Imatinib Mesylate / administration & dosage
  • Imatinib Mesylate / blood*
  • Imatinib Mesylate / pharmacokinetics
  • Kinetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / blood
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / genetics
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / pathology
  • Male
  • Middle Aged
  • Pharmacogenetics*

Substances

  • Imatinib Mesylate