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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Yamakawa, Y. Hamada, A. Shuto, T. Yuki, M. Uchida, T. Kai, H. Kawaguchi, T. Saito, H. |
| Description | Country affiliation: Japan Author Affiliation: Yamakawa Y ( Department of Clinical Pharmaceutical Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan.) |
| Abstract | 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. |
| File Format | HTM / HTML |
| ISSN | 00099236 |
| Issue Number | 1 |
| Volume Number | 90 |
| e-ISSN | 15326535 |
| Journal | Clinical Pharmacology & Therapeutics |
| Language | English |
| Publisher | Wiley |
| Publisher Date | 2011-07-01 |
| Publisher Place | United States |
| Access Restriction | One Nation One Subscription (ONOS) |
| Subject Keyword | Discipline Pharmacology Antineoplastic Agents Pharmacokinetics Leukemia, Myelogenous, Chronic, Bcr-abl Positive Genetics Metabolism Organic Anion Transporters Piperazines Pyrimidines Algorithms Therapeutic Use Antioxidants Pharmacology Benzamides Blotting, Western Caco-2 Cells Dna Epithelium Flavanones Genotype Hek293 Cells Humans Imatinib Mesylate K562 Cells Drug Therapy Polymorphism, Genetic Reverse Transcriptase Polymerase Chain Reaction Journal Article Research Support, Non-u.s. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
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