Hiwa SabirKidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys are functioning at less than 15% of normal. Many drugs and their metabolites undergo renal excretion and therefore accumulate in renal failure. The selection of a safe and effective drug regimen for patients with renal impairment can be difficult.
Drug Metabolism
Is a process that alters the pharmacological activity and rate of excretion of a drug. It consists of reactions such as oxidation and reduction in which a new functional group is created, and conjugation reactions in which substances such as glucuronic acid, sulphate or amino acids are added to the molecule. The product of metabolism is generally inactive and water soluble, and can be excreted in either the urine or the bile.
Renal Disease
Will perturb the disposition of drugs that primarily depend upon renal excretory function for elimination. While changes in drug half-life (T1/2) are often cited as evidence of altered drug disposition, it must be remembered that T1/2 is a dependent variable whose magnitude varies directly with volume of distribution (Vd) and indirectly with total body clearance (CIT).
Renal failure may influence hepatic drug metabolism either by inducing or inhibiting hepatic enzymes, or by its effects on other variables such as protein binding, hepatic blood flow and accumulation of metabolites. If the metabolism of a drug is known to increase in renal failure, then the dose may have to be increased in order to achieve the therapeutic effect. Conversely, if the metabolism of a drug decreases in renal failure, then a reduction in dose will be necessary to avoid unwanted effects. If the effect of renal failure on the metabolism of a drug is unknown, then particular care should be taken with drugs that are extensively metabolized in the liver and have a narrow therapeutic index.
