Antibiotic efflux pumps in eukaryotic cells: occurrence and impact on antibiotic cellular pharmacokinetics, pharmacodynamics and toxicodynamics

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Abstract
Active efflux is now recognized as a key element in drug disposition and activity. Original observations were first limited to a few compounds examined in specific situations, such as anthracyclines in the context of resistance of cancer cells, and tetracyclines in the context of bacterial resistance. However, the combination of systematic surveys involving commonly used drugs and genome sequencing has identified ∼20 families of drug transporters.1 Many of them are ubiquitous, and are expressed in prokaryotes and archaea as well as in inferior and superior eukaryotes. A companion review2 deals with antibiotic transporters in prokaryotes, where we examine their role and impact on intrinsic antimicrobial activity and resistance. We concentrate here on eukaryotic cells in general, and on animals (including man) in particular, to show how transporters need to be taken into account for a proper understanding as to how antibiotics are handled in vivo.

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