Drug Therapy in Renal Insufficiency and During Dialytic Treatment

Abstract

The persistence of a drug in the body following its absorption depends on factors such as biotransformation, protein binding, sequestration in various organs in the body compartments and excretion into bile, feces and urine. The kidney is the principal organ for termination of drug action via excretion for many commonly used drugs. If a drug is removed from the body mainly via renal elimination, then modification of drug therapy is critical in azotemic patients to insure adequate treatment without producing toxicity [1–3]. As demonstrated in the studies of Richet, de Novales and Verroust [4] and Smith, Seidl and Cluff [5], the incidence of adverse drug reactions is greater in azotemic patients. Ideally, dosage modification in azotemic patients would produce plasma concentration peaks and nadirs which closely mimic those obtained in patients without renal failure. Such an ideal is rarely obtained. However, reasonable clinical goals can be obtained, as the renal elimination of most drugs is closely related to a measure of glomerular filtration rate (GFR) such as the endogenous creatinine clearance [3]. In functionally anephric or anuric patients, drug elimination via non-renal routes and through dialysis (hemo- or peritoneal) becomes paramount.

Supported in part by a grant (RR-133) and the CLINFO Computer System (RR-37) from the General Clinical Research Centers Program of the Division of Research Resources, National Institutes of Health, and by the National Institutes of Health-National Institute of Allergy, Metabolic, and Digestive Diseases, Contract NO1-AM-2–2219