PT  - JOURNAL ARTICLE
AU  - Takanobu Matsuzaki
AU  - Takafumi Morisaki
AU  - Wakako Sugimoto
AU  - Koji Yokoo
AU  - Daisuke Sato
AU  - Hiroshi Nonoguchi
AU  - Kimio Tomita
AU  - Tomohiro Terada
AU  - Ken-ichi Inui
AU  - Akinobu Hamada
AU  - Hideyuki Saito
TI  - Altered Pharmacokinetics of Cationic Drugs Caused by Down-Regulation of Renal Rat Organic Cation Transporter 2 (<em>Slc22a2</em>) and Rat Multidrug and Toxin Extrusion 1 (<em>Slc47a1</em>) in Ischemia/Reperfusion-Induced Acute Kidney Injury
AID  - 10.1124/dmd.107.019869
DP  - 2008 Apr 01
TA  - Drug Metabolism and Disposition
PG  - 649--654
VI  - 36
IP  - 4
4099  - http://dmd.aspetjournals.org/content/36/4/649.short
4100  - http://dmd.aspetjournals.org/content/36/4/649.full
SO  - Drug Metab Dispos2008 Apr 01; 36
AB  - In the proximal tubules of rat (r) kidney, the polyspecific organic cation transporters (OCTs), rOCT1 and rOCT2, mediate the baso-lateral uptake of various organic cations, including many drugs, toxins, and endogenous compounds, and the apical type of H+/ organic cation antiporter, rat multidrug and toxin extrusion 1 (rMATE1), mediate the efflux of organic cations. Renal clearances of H2 receptor antagonists, including famotidine, were reported to be decreased in patients with kidney disease. Therefore, acute kidney injury (AKI) could influence renal excretion and disposition of organic cations accompanied by the regulation of organic cation transporters. The aim of this study was to investigate the pharmacokinetic alteration of cationic drugs and the expression of tubular organic cation transporters, rOCT1, rOCT2, and rMATE1, in ischemia/reperfusion (I/R)-induced AKI rats. I/R-induced AKI increased the plasma concentration of i.v. administrated famotidine, a substrate for rOCT1 and rOCT2, or tetraethylammonium (TEA), a substrate for rOCT1, rOCT2, and rMATE1. The areas under the plasma concentration curves for famotidine and TEA were 2- and 6-fold higher in I/R rats than in sham-operated rats, respectively. The accumulation of TEA into renal slices was significantly decreased, suggesting that organic cation transport activity at the basolateral membranes was reduced in I/R rat kidney. The protein expressions of basolateral rOCT2 and luminal rMATE1 were down-regulated in I/R rat kidneys. These data suggest that the urinary secretion of cationic drugs via epithelial organic cation transporters is decreased in AKI.