Metabolism of Drugs in Patients with Renal Insufficiency



With the development of renal insufficiency, there is a decrease in glomerular filtration as well as a loss of secretory and absorptive transport functions of the kidney. These changes in renal function may have a major effect on the kinetics of drugs that are excreted by the kidney. In ad­dition, renal failure is characterized by the reten­tion of endogenous organic compounds in the blood. Some of these compounds may compete with the pharmacological agents for specific renal transport systems.

Renal insufficiency may affect the metabolism of drugs not only by decreasing the rates of ex­cretion in the urine, but also by a number of non­renal mechanisms. Renal disease is associated with alterations in the binding of drugs by plasma proteins and, as a consequence, may affect the bioavailability of some drugs. An example of such a change in bioavailability is the pharmacokinet­ics of Dilantin (phenytoin) in renal failure pa­tients. Presumably owing to occupancy by some products retained in uremia, Dilantin is less av­idly bound by plasma proteins and the free con­centration of the drug is increased. Renal insuf­ficiency may be associated with a change in the volume of distribution of certain drugs. The ab­sorption of drugs form the gastrointestinal tract may be impaired in patients with renal disease. The secondary consequences of renal failure may also alter the metabolic pathways of drugs in other organs.