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Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid leukemia 山川, 裕司 111943 濱田, 哲暢 111944 首藤, 剛 111945 結城, 美里 111946 内田, 隆 111947 甲斐, 広文 111948 川口, 辰哉 111949 齋藤, 秀之 111950 Yamakawa, Yuji 111927 濱田, 哲暢 98305 ハマダ, アキノブ Hamada, Akinobu Shuto, Tsuyoshi 111929 Yuki, Misato 111930 Uchida, Takashi 111931 Kai, Hirofumi 111932 Kawaguchi, Tatsuya 111933 Saito, Hideyuki 111934 499 imatinib SLCO1A2 polymorphisms pharmacogenetics application/pdf 論文(Article) The purpose of this study was to explore the role of the organic-anion transporting polypeptide (OATP) 1A2 that 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 chronic myeloid leukemia (CML) patients. 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, the human intestinal cell line Caco-2, and the CML cell line K562 cells. Linkage disequilibrium was found between the SLCO1A2 -1105G>A and -1032G>A genotypes in 34 CML patients and 100 healthy subjects. Imatinib clearance of 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. http://www.nature.com/clpt/journal/v90/n1/full/clpt2011102a.html journal article Nature Publishing Group 2011-07-01 AM application/pdf Clinical Pharmacology and Therapeutics 1 90 157 163 https://kumadai.repo.nii.ac.jp/record/24853/files/CPT_90_1_157–163.pdf http://hdl.handle.net/2298/23261 https://kumadai.repo.nii.ac.jp/records/24853 eng 00099236 © 2011 American Society for Clinical Pharmacology and Therapeutics