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Clin Pharmacol Ther. 2011 Jul;90(1):157-63. doi: 10.1038/clpt.2011.102. Epub 2011 Jun 1.

Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid leukemia.

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Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.


The purpose of this study was to explore the role of the organic anion-transporting polypeptide (OATP) 1A2, which is encoded by SLCO1A2, in the cellular uptake of the Bcr-Abl tyrosine kinase inhibitor imatinib, and the relationship between SLCO1A2 polymorphisms and the pharmacokinetics of imatinib in patients with chronic myeloid leukemia (CML). Imatinib uptake was significantly enhanced in OATP1A2-transfected human embryonic kidney (HEK) 293 cells (P = 0.002). Naringin, an OATP1A2 inhibitor, decreased the transport of imatinib in OATP1A2-transfected HEK293 cells, the human intestinal cell line Caco-2, and K562 CML cells. Linkage disequilibrium was found between the SLCO1A2 -1105G>A and -1032G>A genotypes in 34 CML patients and 100 healthy subjects. Imatinib clearance in CML patients was influenced by the SLCO1A2 -1105G>A/-1032G>A genotype (P = 0.075) and the SLCO1A2 -361GG genotype (P = 0.005). These findings suggest that imatinib is transported into cells by OATP1A2, and that SLCO1A2 polymorphisms significantly affect imatinib pharmacokinetics.

[Indexed for MEDLINE]

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