The renal secretion of many drugs is facilitated by membrane transporters, including organic cation transporter 2, multidrug and toxin extrusion protein 1/2-K and organic anion transporters 1 and 3. Inhibition of these transporters can reduce renal excretion of drugs and thereby pose a safety risk. Assessing the risk of inhibition of these membrane transporters by investigational drugs remains a key focus in the evaluation of drug-drug interactions (DDIs). Current methods to predict DDI risk are based on generating in vitro data followed by a clinical assessment using a recommended exogenous probe substrate for the individual drug transporter. More recently, monitoring plasma-based and urine-based endogenous biomarkers to predict transporter-mediated DDIs in early phase I studies represents a promising approach to facilitate, improve and potentially avoid conventional clinical DDI studies. This perspective reviews the evidence for use of these endogenous biomarkers in the assessment of renal transporter-mediated DDI, evaluates how endogenous biomarkers may help to expand the DDI assessment toolkit and offers some potential knowledge gaps. A conceptual framework for assessment that may complement the current paradigm of predicting the potential for renal transporter-mediated DDIs is outlined.
© 2024. The Author(s).