Mechanisms and clinical implications of renal drug excretion.
The body defends itself against potentially harmful compounds like drugs, toxic compounds, and their metabolites by elimination, in which the kidney plays an important role. Renal clearance is used to determine renal elimination mechanisms of a drug, which is the result of glomerular filtration, active tubular secretion and reabsorption. The renal proximal tubule is the primary site of carrier-mediated transport from blood to urine. Renal secretory mechanisms exists for, anionic compounds and organic cations. Both systems comprises several transport proteins, and knowledge of the molecular identity of these transporters and their substrate specificity has increased considerably in the past decade. Due to overlapping specificities of the transport proteins, drug interactions at the level of tubular secretion is an event that may occur in clinical situation. This review describes the different processes that determine renal drug handling, the techniques that have been developed to attain more insight in the various aspects of drug excretion, the functional characteristics of the individual transport proteins, and finally the implications of drug interactions in a clinical perspective.
Masereeuw
R
R
Department of Pharmacology and Toxicology, University Medical Centre Nijmegen, The Netherlands.
Russel
F G
FG
D000818:Animals; D006801:Humans; D007668:Kidney / Q000378:metabolism* / Q000502:physiology; D004364:Pharmaceutical Preparations / Q000378:metabolism*
D004364:Pharmaceutical Preparations