Different Involvement of OAT in Renal Disposition of Oral Anticoagulants Rivaroxaban, Dabigatran, and Apixaban.
Different Involvement of OAT in Renal Disposition of Oral Anticoagulants Rivaroxaban, Dabigatran, and Apixaban.
复制标题
OAT 在口服抗凝剂利伐沙班、达比加群和阿哌沙班的肾脏处置中的不同参与。
DOI：
10.1016/j.xphs.2017.04.044
复制
发表时间：
2017
影响因子：
3.8
通讯作者：
I. Tamai
中科院分区：
文献类型：
--
作者：
Yuri Tsuruya;T. Nakanishi;Hisakazu Komori;Xinying Wang;N. Ishiguro;Tomoko Kito;Kouji Ikukawa;W. Kishimoto;Sumito Ito;O. Schaefer;T. Ebner;N. Yamamura;H. Kusuhara;I. Tamai
This study aimed to investigate the interactions of 3 anticoagulants, rivaroxaban, apixaban, and dabigatran, with 5 human solute carrier transporters, hOAT1, hOAT3, hOCT2, hOATP1B1, and hOATP1B3. Apixaban inhibited hOAT3, hOATP1B1, and hOATP1B3, and rivaroxaban inhibited hOAT3 and hOATP1B3, with IC50values of >20 and >5 μM, respectively. The effect of dabigatran was negligible or very weak, so significant drug interactions at therapeutic doses are unlikely. Specific uptake of rivaroxaban was observed only in human and mouse OAT3-expressing cells. TheKmfor mouse Oat3 (mOat3) was 1.01 ± 0.70 μM. A defect in mOat3 reduced the kidney-to-plasma concentration ratio of rivaroxaban by 38% in mice. Probenecid treatment also reduced the kidney-to-plasma concentration ratio of rivaroxaban in rats by 73%. Neither mOat3 defect nor probenecid administration in rats reduced the renal clearance of rivaroxaban. The uptake of rivaroxaban by monkey kidney slices was temperature dependent and inhibited by probenecid but not by tetraethylammonium. Taken together, organic anion transporters, mainly OAT3, may mediate basolateral uptake of rivaroxaban in kidneys. hOAT3 could be an additional factor that differentiates the potential drug-drug interactions of the 3 anticoagulants in the urinary excretion process in clinical settings.
DOI：
10.1248/bpb1978.4.879
发表时间：
1981-01-01
期刊：
JOURNAL OF PHARMACOBIO-DYNAMICS
影响因子：
--
作者：
YAMAOKA, K;TANIGAWARA, Y;UNO, T
通讯作者：
UNO, T
DOI：
10.1124/jpet.104.068056
发表时间：
2004-10-01
影响因子：
3.5
作者：
Hirano, M;Maeda, K;Sugiyama, Y
通讯作者：
Sugiyama, Y
DOI：
10.1124/jpet.106.113076
发表时间：
2007-04-01
影响因子：
3.5
作者：
Nozaki, Yoshitane;Kusuhara, Hiroyuki;Sugiyama, Yuichi
通讯作者：
Sugiyama, Yuichi