RENAL METABOLISM Of DRUGS



A large number of drugs are eliminated from the body by renal excretion. Excretion of drugs by the kidney may involve filtration, secretion, and reab-sorption depending upon the agent in question. Filtration of a drug through the glomerulus de­pends on the chemical characteristics of the drug itself and the degree of binding of the drug to plasma proteins. Drugs that are highly bound to plasma proteins are poorly filtered, while those that are bound less avidly or not at all can gain access to the tubular fluid. Drugs that are organic anions or cations can be secreted from the peri­tubular capillary blood into the lumen of the tub­ule by specific transport mechanisms in renal tu­bular cells. Some drugs that gain access to the tubular fluid by filtration and/or secretion may be reabsorbed back into the systemic circulation by mediated or passive transport mechanisms. For some drugs, bidirectional transport across renal tubules is known to occur, so that the net rate of excretion is dependent on the relative activities of the secretory and absorptive processes. For or­ganic anions and cations whose pK is in the range of the pH normally attainable in the tubular fluid, any change in the pH of the urine may have aprofound and clinically important effect on the rate of excretion of the drug. These principles are known as the effects of “nonionic diffusion” and indicate the differences in the permeabilities of drugs across renal membranes when the drug is in its ionized or un-ionized form (Table 35-1}. Alkalinization of the urine significantly increases the excretion of organic anions such as aspirin and phenobarbital. Acidification of the urine in­creases the renal excretion of organic bases such as amphetamines.

In addition to modulating the rates of excretion of drugs, the kidney accumulates certain drugs. The kidney is also capable of metabolizing spe­cific types of pharmaceutical agents. Owing to an effect on specific transport pathways, drug-drug interactions may occur. For example, probenecid, an inhibitor of organic anion secretion, inhibits the tubular secretion of penicillin. Such an inter­action may have clinical utility when it is nec­essary to achieve high blood concentrations of this antibiotic.