Altered pharmacokinetics of cationic drugs caused by down-regulation of renal rat organic cation transporter 2 (Slc22a2) and rat multidrug and toxin extrusion 1 (Slc47a1) in ischemia/reperfusion-induced acute kidney injury

Drug Metabolism and Disposition : the Biological Fate of Chemicals
Takanobu MatsuzakiHideyuki Saito

Abstract

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 H(2) 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...Continue Reading

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Citations

May 16, 2013·Pediatric Nephrology : Journal of the International Pediatric Nephrology Association·Justyna TomczakRobert Milewski
Jul 10, 2008·Pharmaceutical Research·Takafumi MorisakiHideyuki Saito
Aug 12, 2009·Expert Opinion on Drug Metabolism & Toxicology·Edmund Jon Deoon LeeLie Michael George Limenta
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Oct 19, 2019·The Journal of Pharmacology and Experimental Therapeutics·Severin HörmannMichele Visentin
Aug 19, 2020·Journal of Clinical Medicine·Quentin FaucherChantal Barin-Le Guellec
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