Implication of human drug transporters to toxicokinetics and toxicity of pesticides
Abstract
Human membrane drug transporters are recognized as major actors of pharmacokinetics. Pesticides also interact with human drug transporters, which may have consequences for pesticide toxicokinetics and toxicity. The present review summarizes key findings about this topic. In vitro assays have demonstrated that some pesticides, belonging to various chemical classes, modulate drug transporter activity, regulate transporter expression and/or are substrates, thus bringing the proof of concept for pesticide-transporter relationships. The expected low human concentration of pesticides in response to environmental exposure constitutes a key-parameter to be kept in mind for judging the in vivo relevance of such pesticide-transporter interactions and their consequences for human health. Existing data about interactions of pesticides with drug transporters remain, however, rather sparse; more extensive and systematic characterization of pesticide-transporter relationships, through the use of high throughput in vitro assays and/or in silico methods, is, therefore, required. In addition, consideration of transporter polymorphisms, pesticide mixture effects and physiological and pathological factors governing drug transporter expression may help to better define the in vivo relevance of pesticide-transporter interactions in terms of toxicokinetics and toxicity for humans.