Renal tubular handling of drugs

Abstract

The renal excretion of drugs is a vectorial quantity, the resultant of physiologic mechanisms that have directional orientation and magnitude. Magnitude is limited by a variety of extrarenal factors including plasma protein binding and the volume of the total body water. The contributions of the glomeruli and tubules to excretion varies with age. This fact has clinical relevance, especially in newborn children and older patients. Although protein binding reduces the amount of a drug that can be filtered, it usually does not alter the rate of proximal tubular secretion of charged organic molecules. Reabsorption of the filtered fluid from tubular lumens creates concentration gradients favoring the reabsorption of drugs, but the movement of drug molecules out of luminal fluid is hindered by the formation of polar drug metabolites in the liver. Although there are only a few examples in the literature, it is probable that many drugs are reabsorbed by a carrier-mediated process located in the proximal tubules. A major difference exists between the renal handling of chlormerodrin, a neutral mercurial, and of mersalyl, an acidic mercurial. Chlormerodrin is reabsorbed (as a complex with cysteine) by a carrier-mediated process; mersalyl is secreted by one of the organic anion transport systems.