Organic anion and cation transporters are possibly involved in renal excretion of entecavir in rats

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Title Organic anion and cation transporters are possibly involved in renal excretion of entecavir in rats
Author Yanxiao, Chen; Ruijuan, Xu; Jin, Yang; Lei, Chen; Qian, Wang; Xuefen, Yin; Hong, Tang; Xueying, Zhang; Davey, Andrew; Jiping, Wang
Journal Name Life Sciences
Year Published 2011
Place of publication United States
Publisher Elsevier Inc.
Abstract Aims The purpose of the present study was to investigate the roles of transporters in the renal excretion of entecavir. Main methods We analyzed the effect of probenecid, cimetidine, sulfobromophthalein sodium (BSP), verapamil, inhibitors of organic anion transporter (OAT), organic cation transporter (OCT), multidrug resistance-associated protein 2 (MRP2) and P-glycoprotein respectively, on the excretion of entecavir. The area under plasma concentration–time curve (AUC), body clearance, and renal clearance of entecavir was examined in each group. Key findings After intravenous coadministration with entecavir in conscious rats, cimetidine, probenecid, BSP and verapamil significantly increased the AUC of entecavir by 40.07%, 48.78%, 37.49%, and 54.58%, and reduced the body clearance by 27.14%, 31.69%, 29.79%, and 42.17%, respectively. Then the effects of these inhibitors on the renal clearance of entecavir in unconscious rats were studied. Coadministration of cimetidine and probenecid increased the steady plasma concentration of entecavir by 127.61% and 169.46%, reduced the renal clearance by 50.47% and 67.76%, and decreased the excretion ratio by 44.81% and 64.16% compared to initial values. However, the effects of BSP and verapamil were slight. Cimetidine and probenecid also increased the concentration of entecavir in kidney from 34.00 ± 0.80 ng/mL to 55.19 ± 4.92 ng/mL and 49.92 ± 1.53 ng/mL, while the concentration of entecavir in kidney from BSP and verapamil groups was 30.96 ± 0.81 ng/mL and 35.72 ± 7.30 ng/mL, respectively. Significance These results suggest that cimetidine and probenecid inhibit the renal excretion of entecavir in rats, which indicates the most likely involvement of organic anion and cation transporters in the renal excretion of entecavir.
Peer Reviewed Yes
Published Yes
Alternative URI http://dx.doi.org/10.1016/j.lfs.2011.03.018
Volume 89
Issue Number 1-2
Page from 1
Page to 6
ISSN 0024-3205
Date Accessioned 2011-07-27
Date Available 2011-10-07T04:28:39Z
Language en_AU
Research Centre Molecular Basis of Disease
Faculty Griffith Health Faculty
Subject Pharmacology and Pharmaceutical Sciences
URI http://hdl.handle.net/10072/41183
Publication Type Journal Articles (Refereed Article)
Publication Type Code c1x

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