Renal excretion of drugs: tubular transport and metabolism.

Abstract

The regulatory control of renal excretion of drugs and autopharmaco­ logical agents results from either renal tubular reabsorption of filtered so­ lutes or the excretion of solutes into the lumen from peritubular blood. These tubular processes may be active transport processes or passive non­ ionic diffusion of lipid soluble substrates. Many drugs and autopharmaco­ logical agents such as biogenic amines are ionized at body pH and are rela­ tively nonpermeant, but they are moved into and out of cells in directions opposite to their electrochemical gradients. These active transport processes across the renal tubule membrane have been demonstrated for organic ca­ tions such as tetraethylammonium (TEA) and catecholamines and for or­ ganic anions such as p-aminohippurate (PAR) and uric acid. The organic anion and cation transport systems are separate mechanisms which do not demonstrate mutual inhibition. The predominant transport of most organic ions in the renal tubule is in the secretory direction, which is in a direction opposite to the simultaneous movement of the inorganic cation, sodium. Specific examples of the selective tubular control of the excretion of certain drugs and autopharmacological agents will be described in this review. In­ creasing evidence is appearing that for some substances active transport can occur in the directions of both tubular excretion and tubular reabsorption; the amount appearing in the urine is the net result of these two opposing processes. Evidence for some bidirectional transports wilI be detailed in this review. Intrarcnal metabolism may modify the transport of drugs and autophar­ macological agents. A drug may be transported into the renal tubular cell from the blood in one ionized form, be metabolized in the cell into a more polar compound of the same charge, to a neutral molecule, or to an oppo­ sitely charged compound. The metabolite will leave the cell by active trans­ port or down a. concentration gradient if it is diffusible. Active membrane transports of organic ions across the renal tubule may