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  • Title: Renal transporters in drug disposition, drug-drug interactions, and nephrotoxicity.
    Author: Feng B, El-Kattan AF, Radi ZA.
    Journal: Curr Protoc Toxicol; 2012 Aug; Chapter 23():Unit 23.3.1-15. PubMed ID: 22896010.
    Abstract:
    This unit describes in detail the in vitro methods for measuring the interaction of new chemical entities (NCEs) with human renal transporters (hOAT1, hOAT2, and hOCT2) as both a substrate and inhibitor. Renal transporter substrate assays help in the identification of renal secretion mechanisms and assessment of the potential renal drug-drug interactions (DDIs) for NCE as a target, as well as to predict its renal clearance in humans. Human renal transporter (hOAT1, hOAT2, and hOCT2) inhibition assays characterize the inhibition potency of NCE and predict the potential for renal DDIs as a perpetrator with xenobiotics and drugs that are mainly renally cleared. In addition, such inhibition assays enable a better assessment of the potential for renal transporter-mediated nephrotoxicity and pathology. Therefore, renal transporter substrate and inhibition assays are pivotal in drug discovery and development for renally cleared drugs and those that are co-administered with marketed compounds mainly eliminated via the kidney.
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