Imatinib inhibition of fludarabine uptake in T-lymphocytes

Erica L. Woodahl, Joanne Wang, Shelly Heimfeld, Aaron G. Ren, Jeannine S. McCune

Research output: Contribution to journalArticlepeer-review

Abstract

Purpose: We investigated the potential drug-drug interaction between imatinib and fludarabine, which may be concomitantly administered in chronic myeloid leukemia (CML) patients receiving fludarabine-based conditioning for allogeneic hematopoietic cell transplantation (HCT). Imatinib is an inhibitor of human equilibrative transporters (hENTs), which are responsible for the intracellular uptake of fludarabine. Methods: Intracellular accumulation of fludarabine triphosphate (F-ara-ATP), the active metabolite of fludarabine, was measured in CD4+ and CD8+ T-lymphocytes isolated from healthy volunteers, which were treated in vitro with fludarabine alone, and in the presence of either imatinib or NBMPR, a known hENT inhibitor. Results: Imatinib significantly inhibited F-ara-ATP accumulation in CD4+ and CD8+ T-lymphocytes in a concentration-dependent manner. The observed imatinib inhibition was comparable to inhibition observed with NBMPR. The inhibition of F-ara-ATP by imatinib is likely due to inhibition of nucleoside transporters hENT1 and hENT2. Conclusions: There is significant in vitro drug interaction between imatinib and fludarabine. This effect may be of important consideration in patients receiving fludarabine-based conditioning prior to HCT.

Original languageEnglish
Pages (from-to)735-739
Number of pages5
JournalCancer Chemotherapy and Pharmacology
Volume62
Issue number4
DOIs
StatePublished - Sep 2008

Keywords

  • Chronic myeloid leukemia
  • Fludarabine
  • Hematopoietic cell transplantation
  • Imatinib
  • Nucleoside transporters

Fingerprint

Dive into the research topics of 'Imatinib inhibition of fludarabine uptake in T-lymphocytes'. Together they form a unique fingerprint.

Cite this