➦ The Role of OAT1 in the Kidney and Regulatory Considerations for New Drugs

Organic anion transporter 1 (OAT1) is a crucial transporter located on the basolateral membrane of renal proximal tubular cells. It plays a key role in the renal excretion of endogenous metabolites, xenobiotics, and a wide range of therapeutic drugs, including antivirals, antibiotics, and chemotherapeutics. By mediating the uptake of organic anions from the bloodstream into tubular cells, OAT1 significantly influences the clearance of drugs, their systemic exposure, and potential drug–drug interactions. Dysregulation or inhibition of OAT1 can lead to altered pharmacokinetics, nephrotoxicity, or the accumulation of toxic metabolites.

Recognizing its importance, regulatory agencies such as the U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) recommend evaluating new molecular entities for their interaction with OAT1 during preclinical and clinical development. These guidelines aim to predict potential renal drug–drug interactions, assess safety risks, and optimize dosing regimens, ensuring that new therapeutics are both effective and safe for patients. Consequently, OAT1 studies have become a standard component of drug development programs targeting renal excretion pathways.