Solute carrier family 22 member 2 (OCT2) and Multidrug and toxin extrusion protein 1 (MATE1) (OCT2/MATE1)

Gepotidacin is a novel triazaacenaphthylene antibiotic that targets bacterial DNA gyrase and topoisomerase IV, offering a unique mechanism to combat multi-drug resistant infections such as gonorrhea and uncomplicated urinary tract infections (Tiffany et al., 2019). A significant portion of gepotidacin is eliminated through the kidneys via active tubular secretion, a process mediated by specific transport proteins. The primary transporters involved are the Organic Cation Transporter 2 (OCT2), located on the basolateral membrane, and the Multidrug and Toxin Extrusion proteins (MATE1 and MATE2-K), located on the apical membrane of renal proximal tubule cells (UniProt P08173; UniProt Q96FL8). Cimetidine, a histamine H2-receptor antagonist, serves as a potent inhibitor of these transporters and is used in clinical trials to evaluate the impact of transporter-mediated drug-drug interactions (DDIs). When co-administered, cimetidine inhibits the renal secretion of gepotidacin, leading to a significant increase in its systemic exposure (AUC) and a corresponding decrease in renal clearance (Tiffany et al., 2019). This interaction is a critical consideration for the clinical use of gepotidacin, as it necessitates awareness of potential DDIs with other medications that utilize or inhibit the OCT2 and MATE pathways. Monitoring for changes in drug efficacy or toxicity is essential when such combinations are used in clinical practice.

Other names

SLC22A2SLC47A1Organic cation transporter 2Multidrug and toxin extrusion protein 1MATE1OCT2MATE2-KSLC47A2Solute carrier family 47 member 2

Cimetidine acts as a competitive inhibitor of the Organic Cation Transporter 2 (OCT2) and Multidrug and Toxin Extrusion (MATE) proteins, thereby reducing the renal tubular secretion of substrate drugs like gepotidacin.