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Updated: Jul 15, 2026

A Method for Screening and Validation of Resistant Mutations Against Kinase Inhibitors
Published on: December 7, 2014
Imatinib disposition and ABCB1 (MDR1, P-glycoprotein) genotype
H Gurney1, M Wong, R L Balleine
1Department of Medical Oncology, Westmead Hospital Sydney West Area Health Service, Westmead, New South Wales, Australia. howard_gurney@wmi.usyd.edu.au
Abstract:
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.
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