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

• Yamakawa, Yuji

• Hamada, Akinobu

• Shuto, Tsuyoshi

• Yuki, Misato

• Uchida, Takashi

• Kai, Hirofumi

• Kawaguchi, Tatsuya

• Saito, Hideyuki

• 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

Abstract

type: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.

source:00099236

identifier:http://www.nature.com/clpt/journal/v90/n1/full/clpt2011102a.html

Journal

• Clinical Pharmacology and Therapeutics

  Clinical Pharmacology and Therapeutics 90 (1), 157-163, 2011-07-01

  Nature Publishing Group

Keywords

• imatinib
• SLCO1A2
• polymorphisms
• pharmacogenetics
• 499

Details

• CRID: 1050564287882077952
• NII Article ID: 120005952465
• Web Site: http://hdl.handle.net/2298/23261
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • CiNii Articles