Imatinib disposition and ABCB1 (MDR1, P-glycoprotein) genotype

H. Gurney*, M. Wong, R. L. Balleine, L. P. Rivory, A. J. McLachlan, J. M. Hoskins, N. Wilcken, C. L. Clarke, G. J. Mann, M. Collins, S. E. Delforce, K. Lynch, H. Schran

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

126 Citations (Scopus)


The aim of this study was to explore the impact of individual variation in drug elimination on imatinib disposition. Twenty-two patients with gastrointestinal stromal tumor or chronic myeloid leukemia initially received imatinib 600 mg daily with dosage subsequently toxicity adjusted. Pharmacokinetic parameters on day 1 and at steady-state were compared with elimination phenotype and single-nucleotide polymorphisms of CYP3A5 and ABCB1. A fivefold variation in estimated imatinib clearance (CL/F) was present on day 1 and mean CL/F had fallen by 26% at steady state. This reduction in imatinib CL/F was associated with ABCB1 genotype, being least apparent in thymidine homozygotes at the 1236T>C, 2677G>T/A and 3435C>T loci. Toxicity-related dose reduction also tended to be less common in these individuals. ABCB1 genotype was associated with steady-state CL/F due to an apparent genotype-specific influence of imatinib on elimination. Further evaluation of ABCB1 genotype and imatinib dosage is warranted.

Original languageEnglish
Pages (from-to)33-40
Number of pages8
JournalClinical Pharmacology and Therapeutics
Issue number1
Publication statusPublished - 14 Jul 2007
Externally publishedYes


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