Environmental chemicals as substrates, inhibitors or inducers of drug transporters: implication for toxicokinetics, toxicity and pharmacokinetics

Abstract

Introduction: Membrane drug transporters are well recognized as important contributing factors to pharmacokinetics, notably involved in drug–drug interactions. Besides drugs, environmental chemicals, to which humans are commonly exposed, are also substrates, inhibitors or inducers of drug transporters, which may have notable consequences toward toxicokinetics, toxicity and pharmacokinetics. Area covered: This review summarizes key data about the interactions of main environmental contaminants with drug transporters, including the nature of drug transporters involved in contaminant transport, or inhibited or induced by these chemicals. Implications for toxicokinetics and toxicity of pollutants and pharmacokinetics of drugs administrated to pollutant-exposed humans are also discussed. Expert opinion: Although various structurally unrelated environmental chemicals have been already demonstrated to interact with drug transporters, further in vitro and in vivo studies are probably required to characterize pollutant–transporter interplays in a more extensive and accurate way. Data obtained should be next confronted with known exposure levels of humans to pollutants, with the aim to fully determine the relevance of environmental contaminant–transporter interactions in terms of toxicokinetics, toxicity and putative pollutant–drug interactions.