Fluoroquinolone Efflux Mediated by ABC Transporters

Abstract

Quinolones and fluoroquinolones are broad spectrum bactericidal drugs, which are widely used in both human and veterinary medicine. These drugs can quite easily enter cells and are often used to treat intracellular pathogens. Some fluoroquinolones have been reported to undergo efflux, which could explain their low bioavailability. There is a growing need to understand resistance mechanisms to quinolones, involving for instance mutations or the action of efflux pumps. Several members of the ATP-binding cassette (ABC) drug efflux transporter family (MDR, MRP, ABCG2) significantly affect the pharmacokinetic disposition of quinolones. Active secretory mechanisms common to all fluoroquinolones have been suggested, as well as competition between fluoroquinolones at transporter sites. For grepafloxacin and its metabolites, MRP2 has been demonstrated to mediate biliary excretion. However, MDR1 is responsible for grepafloxacin intestinal secretion. Recently it has been shown that ciprofloxacin and enrofloxacin are efficiently transported ABCG2 substrates which are actively secreted into milk. It appears that multiple ABC transporters contribute to the overall secretion of fluoroquinolones. The objective of this work is to review the recent advances in insights into ABC transporters and their effects on fluoroquinolone disposition and resistance including data on drug secretion into milk.