Profiling of a prescription drug library for potential renal drug-drug interactions mediated by the organic cation transporter 2

摘要: Drug-drug interactions (DDIs) are major causes of serious adverse drug reactions. Most DDIs have a pharmacokinetic basis in which one reduces the elimination second drug, leading to potentially toxic levels. As organ elimination, kidney represents an important site for DDIs. Here, we screened prescription library against renal organic cation transporter OCT2/SLC22A2, mediates first step secretion many cationic drugs. Of 910 compounds screened, 244 inhibited OCT2. Computational analyses revealed key properties inhibitors versus noninhibitors, included overall molecular charge. Four six potential clinical were transporter-selective follow-up screens additional transporters: OCT1/SLC22A1, MATE1/SLC47A1, and MATE2-K/SLC47A2. Two showed different kinetics interaction with common polymorphism OCT2-A270S, suggesting role genetics modulating