Chapter 4. Drug Transporters in the Kidney

With a high expression of both uptake and efflux transporters, together with metabolic enzymes, the proximal tubule in the kidney plays a major role in determining the absorption, distribution, metabolism and elimination of a wide range of molecules. Since most members of the solute carrier and ATPase binding cassette families that transport drug molecules in the kidney have broad substrate specificity, there is a need to identify clinically important transporter mediated drug–drug interactions that may result in nephrotoxicity. To address this, efforts have been made to elucidate the mechanisms of drug–drug interactions and toxicity and better understand renal drug transport. The importance of transporters in the kidney has led regulatory agencies around the world to mandate drug–drug interaction and nephrotoxicity safety studies for new molecular entities that have substantial renal elimination. This review summarises the key data on the identification and characterisation of transporters found in the proximal tubule of the kidney. Differences and similarities in transporter expression and function between human and rodent species are also discussed. In addition, current renal in vitro models are explored, along with recent developments in this area.