European Journal of Clinical Pharmacology

, Volume 66, Issue 4, pp 383–386

CYP3A activity influences imatinib response in patients with chronic myeloid leukemia: a pilot study on in vivo CYP3A activity

Authors

  • Henrik Gréen
    • Division of Drug Research/Clinical Pharmacology, Department of Medical and Health Sciences, Faculty of Health SciencesLinköping University
    • Division of Drug Research/Clinical Pharmacology, Department of Medical and Health Sciences, Faculty of Health SciencesLinköping University
  • Franz Rommel
    • Department of HematologyLinköping University Hospital
  • Rajaa A. Mirghani
    • Division of Clinical Pharmacology, Department of Laboratory MedicineKarolinska University Hospital-Huddinge, Karolinska Institute
    • Division of Pharmacology, Faculty of MedicineKing Fahad Medical City
  • Kourosh Lotfi
    • Division of Drug Research/Clinical Pharmacology, Department of Medical and Health Sciences, Faculty of Health SciencesLinköping University
    • Department of HematologyLinköping University Hospital
Pharmacokinetics and Disposition

DOI: 10.1007/s00228-009-0772-y

Cite this article as:
Gréen, H., Skoglund, K., Rommel, F. et al. Eur J Clin Pharmacol (2010) 66: 383. doi:10.1007/s00228-009-0772-y

Abstract

Purpose

Imatinib is currently used for the treatment of chronic myeloid leukemia (CML). The main metabolite CGP74588 has similar potency to that of imatinib and is a product of CYP3A4 and CYP3A5 metabolism. However, the clinical significance of the metabolism on therapeutic response and pharmacokinetics is still unclear. We designed this study to investigate the role of the CYP3A activity in the response to imatinib therapy.

Methods

Fourteen CML patients were phenotyped for in vivo CYP3A activity using quinine as a probe drug. The plasma concentration ratio of quinine and its CYP3A metabolite was used for assessing CYP3A activity. The patients were divided into complete molecular responders with undetectable levels of BCR-ABL transcripts after 12 months of therapy and into partial molecular responders who had failed to achieve a complete molecular response.

Results

Patients that achieved complete molecular response showed significantly (Mann-Whitney U-test, p = 0.013) higher in vivo CYP3A activity (median quinine metabolic ratio = 10.1) than patients achieving partial molecular response (median = 15.9).

Conclusions

These results indicate a clinical significance of the CYP3A activity and its metabolic products in CML patients treated with imatinib.

Keywords

Chronic myeloid leukemia Imatinib CYP3A4 CYP3A5 CGP74588 Complete molecular response

Copyright information

© Springer-Verlag 2009