Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats

Am J Vet Res. 2003 Aug;64(8):994-8. doi: 10.2460/ajvr.2003.64.994.


Objective: To determine bioavailability, pharmacokinetics, and safety for transdermal (TD) and oral administration of fluoxetine hydrochloride to healthy cats.

Animals: 12 healthy mixed-breed sexually intact 1- to 4-year-old purpose-bred cats.

Procedure: A single-dose pharmacokinetic study involving 3 groups of 4 cats each was conducted in parallel. Fluoxetine in a formulation of pluronic lecithin organogel (PLO gel) was applied to the hairless portion of the pinnae of cats at 2 dosages (5 or 10 mg/kg), or it was administered orally in capsules at a dosage of 1 mg/kg. Plasma samples were obtained and submitted for liquid chromatography-mass spectrometry-mass spectrometry analysis of fluoxetine and its active metabolite, norfluoxetine.

Results: Peak fluoxetine concentration (Cmax) was lower and time to Cmax longer for TD administration versus oral administration. Relative bioavailability of each dose administered via the TD route was 10% of the value for oral administration of the drug. Mean plasma elimination half-life after oral administration was 47 and 55 hours for fluoxetine and norfluoxetine, respectively.

Conclusions and clinical relevance: This study provides evidence that fluoxetine in a 15% (wt:vol) PLO gel formulation can be absorbed through the skin of cats into the systemic circulation. However, the relative bioavailability for TD administration is approximately only 10% of that for the oral route of administration.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Cutaneous
  • Administration, Oral
  • Animals
  • Biological Availability
  • Cats / blood
  • Cats / metabolism*
  • Dose-Response Relationship, Drug
  • Fluoxetine / administration & dosage*
  • Fluoxetine / analogs & derivatives*
  • Fluoxetine / blood
  • Fluoxetine / metabolism
  • Fluoxetine / pharmacokinetics*
  • Half-Life
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Serotonin Uptake Inhibitors / blood
  • Serotonin Uptake Inhibitors / metabolism
  • Serotonin Uptake Inhibitors / pharmacokinetics*


  • Serotonin Uptake Inhibitors
  • Fluoxetine
  • norfluoxetine