Renal tubular transporters and antiviral drugs: an update.
Systemic disposition of antiviral drugs partly depends on renal handling of these compounds. There are some known, functionally characterized anionic and cationic transporters with varying substrate specificities for those drugs: human organic anion transporter (OAT) family (hOAT1-3) and human organic cation transporter (OCT) family (hOCT1-3), which mediate the intracellular flux, and adenosine 5'-triphosphate (ATP) binding cassette transporter family (P-glycoprotein, MRP2-5), which mediate the cellular efflux of antiviral drugs. The peptide transporter (PEPT1-2) mediate bi-directional facilitated diffusion of valacyclovir. All these transporters are expressed in the kidney. Organic anion and cation transporters primarily localize to the basolateral membrane of renal epithelial cells while ATP-binding cassette transporters primarily localize to the apical membrane. These transporters work in concert to mediate renal intracellular concentration of occurring antiviral drugs. Along with drug-metabolizing enzymes, these transporters are important determinants of drug effectiveness and toxicity. This review examines the role that these transporters play in renal disposition of antiviral drugs.
Izzedine
Hassane
H
Launay-Vacher
Vincent
V
Deray
Gilbert
G
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000998:Antiviral Agents / Q000493:pharmacokinetics*; D002462:Cell Membrane / Q000378:metabolism; D017320:HIV Protease Inhibitors / Q000493:pharmacokinetics; D006801:Humans; D007684:Kidney Tubules / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D027361:Organic Anion Transporters / Q000378:metabolism*; D027701:Organic Cation Transport Proteins / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000493:pharmacokinetics; D027981:Symporters / Q000378:metabolism
D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters; D000998:Antiviral Agents; D017320:HIV Protease Inhibitors; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; D018894:Reverse Transcriptase Inhibitors; D027981:Symporters