THE EFFECTS OF RENAL AND HEPATIC-DISEASE ON THE PHARMACOKINETICS, RENAL TOLERANCE, AND RISK-BENEFIT PROFILE OF FLUOXETINE

Renal and hepatic diseases have a significant impact on the plasma con centration profiles and the dose requirements for almost all drugs. Th is paper reviews the effect of these diseases and their associated phy siological derangements on the pharmacokinetics of fluoxetine and norf luoxetine. Metabolic studies of fluoxetine in man show that more than 70% of the radiolabelled compound is excreted in the urine. Most of th e urinary radiolabelled products are metabolites and not the parent co mpound nor its active metabolite, norfluoxetine. Cirrhosis of the live r significantly reduces the clearance of fluoxetine and norfluoxetine, but mild, moderate, or severe renal dysfunction does not affect fluox etine or norfluoxetine pharmacokinetics. Daily administration of fluox etine, 20 mg, for more than 2 months to renally impaired, depressed pa tients (who require haemodialysis) produces steady-state fluoxetine an d norfluoxetine plasma concentrations that are comparable to the conce ntrations in depressed patients with normal renal function. Renal func tion is not an important determinant of the steady-state concentration s of fluoxetine or norfluoxetine, though the concentrations may be hig her in patients with significantly impaired liver function.