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oai:kumadai.repo.nii.ac.jp:00024853 2023-09-14T07:09:02Z 413:443

Pharmacokinetic impact of SLCO1A2 polymorphisms on imatinib disposition in patients with chronic myeloid leukemia 山川, 裕司 濱田, 哲暢 首藤, 剛 結城, 美里 内田, 隆 甲斐, 広文 川口, 辰哉 齋藤, 秀之 Yamakawa, Yuji 濱田, 哲暢 ハマダ, アキノブ Hamada, Akinobu 濱田 ハマダ Hamada 哲暢 アキノブ Akinobu Shuto, Tsuyoshi Yuki, Misato Uchida, Takashi Kai, Hirofumi Kawaguchi, Tatsuya Saito, Hideyuki © 2011 American Society for Clinical Pharmacology and Therapeutics 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 Nature Publishing Group 2011-07-01 eng journal article AM http://hdl.handle.net/2298/23261 https://kumadai.repo.nii.ac.jp/records/24853 10.1038/clpt.2011.102 00099236 Clinical Pharmacology and Therapeutics 90 1 157 163 https://kumadai.repo.nii.ac.jp/record/24853/files/CPT_90_1_157–163.pdf application/pdf 218.2 kB 2020-03-02