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• W2017344894 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. Clinical Pharmacology & Therapeutics (2007) 82, 33–40. doi:10.1038/sj.clpt.6100201; published online 9 May 2007" @default.
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• W2017344894 date "2007-05-09" @default.
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• W2017344894 title "Imatinib Disposition and ABCB1 (MDR1, P-Glycoprotein) Genotype" @default.
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• W2017344894 doi "https://doi.org/10.1038/sj.clpt.6100201" @default.
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