Fluoxetine kinetics and protein binding in normal and impaired renal function

Area of Science:

• Pharmacology
• Nephrology
• Clinical Pharmacy

Background:

• Fluoxetine is a widely prescribed antidepressant.
• Renal impairment can affect drug pharmacokinetics.
• The impact of renal dysfunction on fluoxetine disposition requires clarification.

Purpose of the Study:

• To investigate the effect of decreased renal function on fluoxetine and norfluoxetine pharmacokinetics.
• To assess the influence of renal impairment on drug elimination, distribution, and protein binding.
• To determine if hemodialysis alters fluoxetine and norfluoxetine plasma concentrations.

Main Methods:

• Single 40-mg oral dose of fluoxetine administered to 25 adult males.
• Serial blood sampling for 4 weeks to measure fluoxetine and norfluoxetine.
• 24-hour urine collection for 4 weeks to assay drug concentrations.
• Plasma protein binding determined by equilibrium dialysis.
• Noncompartmental pharmacokinetic analysis.

Main Results:

• Fluoxetine and its active metabolite, norfluoxetine, exhibited slow elimination and distribution in a large apparent volume.
• No significant correlation was observed between the degree of renal dysfunction and the rate of elimination, volume of distribution, or protein binding.
• Hemodialysis did not significantly alter plasma concentrations of fluoxetine or norfluoxetine.

Conclusions:

• Decreased renal function does not appear to significantly impact the disposition and elimination of fluoxetine.
• The pharmacokinetic profile of fluoxetine is not substantially altered in patients with impaired kidney function.
• Hemodialysis is unlikely to cause significant changes in fluoxetine or norfluoxetine levels.