Renal Disease Renal excretion of parent drug and metabolites is generally accomplished by glomerular filtration and by specific drug transporters, only now being identified. If a drug or its metabolites are primarily excreted through the kidneys and increased drug levels are associated with adverse effects, drug dosages must be reduced in patients with renal dysfunction to avoid toxicity. The antiarrhythmics dofetilide and sotalol undergo predominant renal excretion and carry a risk of QT prolongation and arrhythmias if doses are not reduced in renal disease. Thus, in end-stage renal disease, sotalol can be given as 40 mg after dialysis (every. | Chapter 005. Principles of Clinical Pharmacology Part 7 Renal Disease Renal excretion of parent drug and metabolites is generally accomplished by glomerular filtration and by specific drug transporters only now being identified. If a drug or its metabolites are primarily excreted through the kidneys and increased drug levels are associated with adverse effects drug dosages must be reduced in patients with renal dysfunction to avoid toxicity. The antiarrhythmics dofetilide and sotalol undergo predominant renal excretion and carry a risk of QT prolongation and arrhythmias if doses are not reduced in renal disease. Thus in end-stage renal disease sotalol can be given as 40 mg after dialysis every second day compared to the usual daily dose 80-120 mg every 12 h. The narcotic analgesic meperidine undergoes extensive hepatic metabolism so that renal failure has little effect on its plasma concentration. However its metabolite normeperidine does undergo renal excretion accumulates in renal failure and probably accounts for the signs of central nervous system excitation such as irritability twitching and seizures that appear when multiple doses of meperidine are administered to patients with renal disease. Protein binding of some drugs . phenytoin may be altered in uremia so measuring free drug concentration may be desirable. In non-end-stage renal disease changes in renal drug clearance are generally proportional to those in creatinine clearance which may be measured directly or estimated from the serum creatinine Chap. 272 . This estimate coupled with the knowledge of how much drug is normally excreted renally vs nonrenally allows an estimate of the dose adjustment required. In practice most decisions involving dosing adjustment in patients with renal failure use published recommended adjustments in dosage or dosing interval based on the severity of renal dysfunction indicated by creatinine clearance. Any such modification of dose is a first approximation and should .
