Publication
Title
Human proximal tubular epithelium actively secretes but does not retain rosuvastatin
Author
Abstract
Rosuvastatin is a potent HMG-CoA reductase inhibitor that has proven to be effective in the treatment of dyslipidemia. Rosuvastatin is cleared from the body by both biliary and renal clearance, the latter believed to be due to active tubular secretion. Whereas the mechanisms of hepatic clearance of rosuvastatin are well documented, those of renal clearance are not. Because rosuvastatin (and other statins) may alter proximal tubular function, this study aimed to characterize the mechanisms of tubular rosuvastatin secretion to define the factors that could influence the presence/concentration of rosuvastatin in proximal tubular cells. Hereto, polarized monolayers of primary human tubular cells were used. We found rosuvastatin net secretion across proximal tubule cells, which was saturable (K-50 = 20.4 +/- 4.1 mu M). The basolateral uptake step was rate-limiting and mediated by OAT3. Rosuvastatin efflux at the apical membrane was mediated by MRP2/4 and ABCG2 together with a small contribution from MDR1 or P-glycoprotein. These data, obtained in an intact human tubule cell model, provide a detailed insight into rosuvastatin's renal handling and the possible factors influencing it.
Language
English
Source (journal)
Molecular pharmacology. - Bethesda, Md
Publication
Bethesda, Md : 2008
ISSN
0026-895X
Volume/pages
(2008), p. 1084-1091
ISI
000259317500016
Full text (Publisher's DOI)
UAntwerpen
Faculty/Department
Research group
Publication type
Affiliation
Publications with a UAntwerp address
External links
Web of Science
Record
Identification
Creation 08.10.2008
Last edited 24.07.2017
To cite this reference