Renal drug-drug interactions: what we have learned and where we are going.

INTRODUCTION: Transporters make a significant contribution to the pharmacokinetic and pharmacodynamic profiles of xenobiotics. The kidney, through the combination of passive glomerular filtration and active tubular secretion, plays an important role in the elimination of some drugs. A growing number of transporter-mediated drug-drug interactions (DDIs) have been described including a subset proposed to occur during the process of active tubular secretion in the renal proximal tubule (PT). AREAS COVERED: An overview of transporters expressed in the human PT is provided. Methodologies for studying transporters are discussed with an emphasis on recent advances in more pharmacologically relevant systems. The molecular mechanisms for known renal DDIs are explored, highlighting commonly implicated transporters. EXPERT OPINION: Clinically relevant renal DDIs are rare. While unlikely to affect most new drug candidates, it is difficult to prospectively predict when renal DDIs are likely to occur. Efforts to identify new transporters and establish predictive model systems have resulted in a rapid evolution in our understanding of renal DDIs. For example, the multidrug and toxin extrusion transporter 1 (MATE1) has emerged as a key transporter in the active tubular secretion of xenobiotics. We are headed toward a time when renal DDIs can be better predicted by preclinical studies.