title: Multidrug and toxin extrusion proteins (MATE/SLC47); role in pharmacokinetics.
abstract: Mammal multidrug and toxin extrusion protein 1 (MATE 1) encoded by SLC47A1 gene was described in 2005 as an efflux transporter that mediates proton-coupled organic cation secretion. Shortly after, other isoforms (MATE2 and MATE2-K, both encoded by SLC47A2 gene) were identified. In the kidney and liver, MATEs work in concert with organic cation transporters (OCTs), together representing an eliminatory pathway for organic cations. Over 40 clinically used drugs and several endogenous compounds are known substrates or inhibitors of MATEs and the list is constantly growing. These transporters are supposed to modulate pharmacokinetics/toxicokinetics and to play a role in drug resistance and (patho)physiological processes. Drug-drug interactions on MATE transporters and polymorphisms in SLC47A genes may affect renal excretion of substrate drugs, such as metformin, resulting in inadequate pharmacotherapy or occurrence of toxic effects. Expression and function of MATEs in tissues other than kidney and liver remain to be elucidated.
authors.affiliation: Department of Pharmacology and Toxicology Charles University in Prague, Faculty of Pharmacy in Hradec Kralove, Hradec Kralove, Czech Republic. frantisek.staud@faf.cuni.cz
authors.forename: Frantisek
authors.initials: F
authors.lastname: Staud
authors.forename: Lukas
authors.initials: L
authors.lastname: Cerveny
authors.forename: Davoud
authors.initials: D
authors.lastname: Ahmadimoghaddam
authors.forename: Martina
authors.initials: M
authors.lastname: Ceckova
mesh_terms: D000818:Animals; D004347:Drug Interactions; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D010599:Pharmacokinetics; D011110:Polymorphism, Genetic
chemical_list: D027701:Organic Cation Transport Proteins; C521869:SLC47A1 protein, human; C521870:SLC47A2 protein, human
keywords: Drug–drug interactions; Efflux transporter; Multidrug and toxin extrusion; Pharmacokinetics