Therapeutic implications of renal anionic drug transporters.
One of most important functions of the kidney concerns the clearance of endogenous waste products, exogenously administered drugs as well as environmental exposures. In addition to glomerular filtration, active tubular secretion is an efficient mechanism for extracting compounds from the circulation and excreting them into the urinary compartment, and it presents one of the determinants of a drug's pharmacokinetic behavior. The renal proximal tubules are equipped with a range of transporters, which can be roughly divided into a system for organic anions and one for organic cations, each consisting of multiple carriers with overlapping substrate specificities that cooperate in basolateral drug uptake and luminal excretion. Drug transporters are often involved in clinically significant drug-drug interactions, leading to unexpected changes in drug plasma levels. Similar effects may be observed for the interaction of drugs with endogenous substrates and food components. Furthermore, disease states could affect the expression and/or function of transport systems as well, mainly through regulation of gene transcription. Finally, inter-individual variability and gender differences exist in the expression of drug transporters, which affect overall renal drug handling. This review highlights recent knowledge of the renal organic anion system with special reference to the therapeutic implications associated with variations in transporter activity and drug interactions.
Dept. of Pharmacology and Toxicology, Radboud University Nijmegen Medical Centre, Nijmegen Centre for Molecular Life Sciences, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
Rosalinde
R
Masereeuw
Frans G M
FG
Russel
D000818:Animals; D027321:Anion Transport Proteins / Q000235:genetics / Q000378:metabolism*; D002908:Chronic Disease; D004347:Drug Interactions; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D007674:Kidney Diseases / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000378:metabolism* / Q000652:urine; D013379:Substrate Specificity
D027321:Anion Transport Proteins; D004364:Pharmaceutical Preparations