Population pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia: results of a phase III study

Br J Clin Pharmacol. 2005 Jul;60(1):35-44. doi: 10.1111/j.1365-2125.2005.02372.x.


Aims: This study was designed to investigate the biochemical and physiological covariates or comedications that affect the pharmacokinetics of imatinib mesylate in patients with chronic-phase chronic myeloid leukaemia (CP CML).

Methods: Pharmacokinetic data were analyzed in 371 patients receiving 400 mg imatinib once daily during a phase III trial of imatinib vs interferon-alfa plus cytarabine for the treatment of newly diagnosed CP CML. Covariates included age, weight, sex, ethnicity, haemoglobin (Hb) concentration, white blood cell (WBC) count, liver function, and creatinine concentration. Blood samples for imatinib analysis were taken on treatment days 1 and 29. Nonlinear mixed effects modelling was used for the population pharmacokinetic analysis.

Results: Population mean estimates (95% confidence interval) at day 1 for apparent clearance (CL) and apparent volume of distribution (V) of imatinib were 14 (13-15) l h(-1) and 252 (237-267) l, respectively. Modelling suggested that CL decreased by 4 (3-5) l h(-1) from day 1 to day 29, whereas V remained unchanged. Interindividual variability in CL and V was 32% and 31%, respectively. Weight, Hb, and WBC count demonstrated small effects on CL and V. Doubling body weight or Hb or halving the WBC count was associated with a 12%, 86% and 8% increase in CL, respectively, and a 32%, 60% and 5% increase in V, respectively. Comedications showed no clear effects on imatinib CL.

Conclusions: Population covariates and coadministered drugs minimally affected imatinib pharmacokinetics in newly diagnosed CP CML patients.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents / pharmacokinetics*
  • Benzamides
  • Female
  • Humans
  • Imatinib Mesylate
  • Leukemia, Myeloid, Chronic-Phase / drug therapy*
  • Leukemia, Myeloid, Chronic-Phase / metabolism
  • Male
  • Middle Aged
  • Piperazines / pharmacokinetics*
  • Pyrimidines / pharmacokinetics*


  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate