Fluoxetine kinetics and protein binding in normal and impaired renal function

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Abstract
The effect of decreased renal function on the disposition and elimination of the nontricyclic antidepressant fluoxetine was examined in 25 adult male subjects after a single 40 mg oral dose. Blood samples for the measurement of fluoxetine and its active metabolite norfluoxetine were drawn 13 times in the first 48 h after dosing and 3 times per wk thereafter for 4 wk. All urine was collected in daily aliquots for 4 wk and was assayed for fluoxetine and norfluoxetine concentrations. The extent of fluoxetine binding to plasma protein was determined by equilibrium dialysis. Kinetic analyses were by noncompartmental methods. The drug and its metabolite were distributed over a large apparent volume and both were eliminated slowly. No correlations between the degree of renal dysfunction and the rate of elimination, volume of distribution or protein binding were found. Plasma concentrations of fluoxetine and norfluoxetine were not significantly changed by hemodialysis.