Rf. Bergstrom et al., THE EFFECTS OF RENAL AND HEPATIC-DISEASE ON THE PHARMACOKINETICS, RENAL TOLERANCE, AND RISK-BENEFIT PROFILE OF FLUOXETINE, International clinical psychopharmacology, 8(4), 1993, pp. 261-266
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.