Imatinib Disposition and ABCB1 (MDR1, P-Glycoprotein) Genotype

• DOI: 10.1038/sj.clpt.6100201
• Publication Date: 2007-05-09T17:09:14Z
• Authors: 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
• Keywords: Stromal tumor; Clinical Pharmacology; P-glycoprotein; Imatinib Mesylate

The aim of this study was to explore the impact individual variation in drug elimination on imatinib disposition. Twenty-two patients with gastrointestinal stromal tumor or chronic myeloid leukemia initially received 600 mg daily dosage subsequently toxicity adjusted. Pharmacokinetic parameters day 1 and at steady-state were compared phenotype single-nucleotide polymorphisms CYP3A5 ABCB1. A fivefold estimated clearance (CL/F) present mean CL/F had fallen by 26% steady state. This reduction associated ABCB1 genotype, being least apparent thymidine homozygotes 1236T>C, 2677G>T/A 3435C>T loci. Toxicity-related dose also tended be less common these individuals. genotype due an genotype-specific influence elimination. Further evaluation is warranted. Clinical Pharmacology & Therapeutics (2007) 82, 33–40. doi:10.1038/sj.clpt.6100201; published online 9 May 2007