Inhibitory potential of tuberculosis drugs on ATP-binding cassette drug transporters
- Brake, L.H. te
- Russel, F.G.
- Heuvel, J.J.T.M.
- Knegt, G.J. de
- Steenwinkel, J.E. de
- Burger, D.M.
- Aarnoutse, R.E.
- Koenderink, J.B.
DOIAbstract
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]-E1S (BCRP); [(3)H]-TCA (BSEP); [(3)H]-E217betaG (MRP1, 3...
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