RENAL DRUG TRANSPORT - A REVIEW

Renal drug elimination involves three major processes: glomerular filt ration, tubular secretion, and tubular reabsorption. Drug filtration i s a simple unidirectional diffusion process. Renal tubular secretion a nd reabsorption are bidirectional processes that often involve both pa ssive diffusion and carrier-mediated membrane processes. Various in vi vo and in vitro techniques are available to study renal drug eliminati on and renal drug transport. The complete renal handling of a drug is best understood from data obtained from a combination of in vivo and i n vitro methodologies. At the membranes of the renal proximal tubule, a number of carrier systems are involved in the tubular secretion and/ or reabsorption of various drugs. Organic acid and base transporters a re two major carrier systems important in the tubular transport of a n umber of organic acid and base drugs, respectively. Nucleoside and P-g lycoprotein transporters appear to play an important role in renal tub ular transport of dideoxynucleosides (e.g., zidovudine, dideoxyinosine ) and digoxin, respectively. Clinically, these transporters are not on ly necessary for the renal tubular secretion and reabsorption of vario us drugs, but are also responsible in part for the drug's pharmacologi c response (e.g., furosemide), drug-drug interactions of therapeutic o r toxic importance, and drug nephrotoxicity.