Solute Carrier (SLC) Family Transporters

Abstract

Xenobiotic transporters are required evaluated by the European and US regulatory agencies for the substrate and inhibition potential of drug candidates, due to the contribution of these to drug‐drug interactions. Interactions involving membrane transporters can alter the blood concentration time profiles of drugs, leading to altered levels of co‐administered drugs. Transporters play a role in toxicities, as inhibition of transporter activity could lead to increased drug concentrations or inhibition clearance of endogenous and exogenous substrates. While the SLC transporter family includes over 300 membrane bound transporters, less than 20 of these are currently considered relevant to drug related interactions. Of these, just eight are recommended by the regulatory agencies ‐ the ABC efflux transporters P‐gp and BCRP and the SLC uptake transporters OATP1B1, OATP1B3, OCT1 and BSEP which are hepatic, and the renal transporters OAT1, OAT3 and OCT2. This chapter discusses the major families of the SLC transporters that are involved in drug transport and provide information on structures, activities, substrates, inhibitors and genetic polymorphisms. Different in vitro and in vivo preclinical models are also discussed, so as to provide a more holistic view of these studies.

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