Update on drug-drug interaction at organic cation transporters: mechanisms, clinical impact, and proposal for advanced testing.

: Organic cation transporters collectively called OCTs belong to three gene families ( OCT1, OCT2, OCT3, OCTN1, OCTN2, PMAT, MATE1, and MATE2-K). OCTs transport structurally diverse drugs with overlapping selectivity. Some OCTs were shown to be critically involved in pharmacokinetics and therapeutic efficacy of cationic drugs. Drug-drug interactions at individual OCTs were shown to result in clinical effects. Procedures for testing of drugs for interaction with OCT1, OCT2, MATE1, and MATE2-K have been recommended.: An overview of functional properties, cation selectivity, location, and clinical impact of OCTs is provided. In addition, clinically relevant drug-drug interactions in OCTs are compiled. Because it was observed that the half maximal concentration of drugs to inhibit transport by OCTs () is dependent on the transported cation and its concentration, an advanced protocol testing of drugs for interaction with OCTs is proposed. In addition, it is suggested to include OCT3 and PMAT for testing.: Research on clinical roles of OCTs should be reinforced including more transporters and drugs. An improvement of the testing protocol considering recent data is imperative for the benefit of patients.