The elimination of drugs from the body by the kidneys involves mainly three processes: glomerular filtration, active tubular secretion and passive tubular reabsorption. Only a few drugs are known to be excreted by glomerular filtration only. These drugs are not handled by the renal tubules and the amount excreted will always be equal to the amount filtered. Drug excretion depends on protein binding but is not influenced by changes of urine flow and urinary pH. Renal excretion will be very ineffective if a drug is highly lipid-soluble, since then the tabular epithelium presents no barrier to back diffusion. The drug concentration in tubule fluid and urine is then close to the concentrations in the extracellular fluid. Clearance, therefore, is always smaller than GFR and depends on urine flow. Drugs which are organic bases or acids may be actively secreted by the proximal tubules. This group comprises a wide variety of clinically important drugs. The transport systems for organic bases and acids can be clearly separated from each other, and most of the proteins mediating transport have now been identified. Within each transport system exists competition for transport, but some drugs can interact with both transporters. Transport completion has important implications for pharmacological drug interaction. Some acid or basic drugs may undergo tubular reabsorption by nonionic diffusion, i.e., reabsorption of the nonionized species only. The amount of the uncharged form present in the tubule fluid and hence tubular drug reabsorption depends on the pKa value of the individual drug and on urinary pH. Some drugs are sequestered within the renal cortex or medulla. Intrarenal accumulation may involve prolonged pharmacological action (diuretics) or nephrotoxicity (antibiotics, analgetics).
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