Theory and practice of tailoring pharmacotherapy in patients with kidney disease

Abstract

When optimizing pharmacotherapy for patients with renal dysfunction, the accurate renal excretion ratio (Rr) of the drug must be known. Rr is the ratio of renal drug clearance to total body drug clearance. The urinary excretion ratio of the unchanged drug (Xu/dose) is required to calculate Rr. Xu/dose is often calculated based on radioactivity excreted in the urine after administration of a radioisotope-labelled drug, taking into account the unmetabolized drug and inactive metabolites together. However, when a fraction of the metabolized drug is high, decreased renal function does not greatly affect the efficacy or safety. Xu/dose needs to be calculated based on the active unchanged drug. The Rr of oral drugs is calculated by Xu/dose divided by bioavailability. If the metabolites of a drug affect its efficacy or toxicity, it is necessary to consider the renal excretion of these metabolites when adjusting drug dosages. If a drug has a long half-life in blood, the evaluation of Xu/dose needs to consider the time required for the drug to be completely excreted from the body. Drug dosages and the frequency of drug administration are adjusted in patients with renal dysfunction to maintain the drug blood exposure comparable to that of patients with normal renal function. While decreasing drug dosages without altering the frequency is relatively simple, a steady drug concentration in the blood is only reached after a prolonged time. This steady state may be reached earlier if the drug is initially administered at a higher dosage. Adjusting the frequency without adjusting the dosage allows maximum and minimum blood concentrations to be modulated so that they are the same as those of patients with normal renal function. These various principles must be considered to effectively tailor drug administration in patients with kidney disease.