Inhibitory potential of tuberculosis drugs on ATP-binding cassette drug transporters

Summary Background Multiple-drug therapy for tuberculosis (TB) and TB-associated co-morbidity increase the likelihood of drug–drug interactions (DDIs). Inhibition of membrane transporters is an important mechanism underlying DDIs. In this study, we assessed the in vitro inhibitory potential of currently used first and second-line TB drugs and of proposed mycobacterial efflux pump inhibitors (EPIs) on the major ABC transporters relevant to drug transport, namely P-gp, BCRP, BSEP and MRP1-5. Methods Membrane vesicles isolated from transporter-overexpressing HEK293 cells were used to study the inhibitory action of TB drugs and EPIs on the transport of model substrates [3 H]-NMQ (P-gp); [3 H]-E1 S (BCRP); [3 H]-TCA (BSEP); [3 H]-E217βG (MRP1, 3 and 4) and [3 H]-MTX (MRP2 and 5). Results A strong inhibition (IC50 value