Interactions of pesticides with membrane drug transporters implications for toxicokinetics and toxicity

Abstract : Drug transporters are now recognized as major actors of pharmacokinetics. They are also likely implicated in toxicokinetics and toxicology of environmental pollutants, notably pesticides, to which humans are widely exposed and which are known to exert various deleterious effects toward health. Interactions of pesticides with drug transporters are therefore important to consider. Areas covered: This review provides an overview of the interactions of pesticides with membrane drug transporters, i.e. inhibition of their activity, regulation of their expression, and handling of pesticides. Consequences for toxicokinetics and toxicity of pesticides are additionally summarized and discussed. Expert opinion: Some pesticides belonging to several chemical classes, such as organochlorine, pyrethroid, and organophosphorus pesticides, have been demonstrated to interact with various uptake and efflux drug transporters, including the efflux pump P-glycoprotein (P-gp) and the uptake organic cation transporters (OCTs). This provides proof of the concept that pesticide-transporter relationships merit attention. More extensive and systematic characterization of pesticide-transporter relationships, possibly through the use of in silico methods, is however likely required. In addition, consideration of transporter polymorphisms, pesticide mixture effects, and realistic pesticide concentrations reached in humans may help better define the in vivo relevance of pesticide-transporter interactions in terms of toxicokinetics and toxicity.
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Lisa Chedik, Arnaud Bruyère, Astrid Bacle, Sophie Potin, Marc Le Vée, et al.. Interactions of pesticides with membrane drug transporters implications for toxicokinetics and toxicity. Expert Opinion on Drug Metabolism and Toxicology, Taylor & Francis, 2018, 14 (7), pp.739-752. ⟨10.1080/17425255.2018.1487398⟩. ⟨hal-01863032v2⟩

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