Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects

Cancer Chemother Pharmacol. 2004 Feb;53(2):102-6. doi: 10.1007/s00280-003-0722-9. Epub 2003 Nov 7.


Objective: This study was carried out to investigate the influence of CYP3A induction with rifampicin on imatinib (Gleevec) exposure.

Methods: The study employed a single center, single-sequence design. A group of 14 healthy male and female subjects received imatinib as a single 400 mg oral dose on two occasions: on study day 1 and on study day 15. Rifampicin treatment (600 mg once daily) for CYP4503A induction was initiated on study day 8 and maintained until day 18. Imatinib pharmacokinetics were determined up to 96 h after dosing on day 1 (no induction) and on days 15-18 (during concomitant rifampicin). Plasma concentrations of imatinib and its main metabolite CGP74588 were determined using a LC/MS/MS method. The ratio of 6beta-hydroxycortisol to cortisol excreted in the urine was measured to monitor the induction of CYP3A.

Results: During concomitant rifampicin administration, the mean imatinib C(max), AUC(0-24) and AUC(0- infinity ) decreased by 54% (90% CI: 48-60%), 68% (64-70%) and 74% (71-76%), respectively. The increase in clearance (Cl/f) was 385% (348-426%) during rifampicin treatment. The mean C(max) and AUC(0-24) of the metabolite CGP74588 increased by 88.6% (68.3%-111.4%) and 23.9% (13.5%-35.2%) after rifampicin pretreatment. However, the AUC(0- infinity ) decreased by 11.7% (3.3-19.4%). All subjects demonstrated a marked induction of hepatic microsomal CYP3A analyzed by the excretion ratio of 6beta-hydroxycortisol to cortisol from a mean baseline concentration of 5.6 U to 50.5 U.

Conclusion: Concomitant use of imatinib and rifampicin or other potent inducers of CYP4503A may result in subtherapeutic plasma concentrations of imatinib. In patients in whom rifampicin or other CYP3A inducers are prescribed, alternative therapeutic agents with less potential for enzyme induction should be selected.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibiotics, Antitubercular / adverse effects
  • Antibiotics, Antitubercular / pharmacology*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics*
  • Area Under Curve
  • Aryl Hydrocarbon Hydroxylases / biosynthesis
  • Benzamides
  • Biotransformation
  • Cytochrome P-450 CYP3A
  • Drug Interactions
  • Enzyme Induction / drug effects
  • Female
  • Half-Life
  • Humans
  • Hydrocortisone / blood
  • Imatinib Mesylate
  • Male
  • Oxidoreductases, N-Demethylating / biosynthesis
  • Piperazines / adverse effects
  • Piperazines / pharmacokinetics*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacokinetics*
  • Rifampin / adverse effects
  • Rifampin / pharmacology*


  • Antibiotics, Antitubercular
  • Antineoplastic Agents
  • Benzamides
  • Piperazines
  • Pyrimidines
  • Imatinib Mesylate
  • Aryl Hydrocarbon Hydroxylases
  • Cytochrome P-450 CYP3A
  • Oxidoreductases, N-Demethylating
  • Rifampin
  • Hydrocortisone