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Accueil veterinaires comportementalistes Veille bibliographique veterinaires comportementalistes Comparative bioavailability of fluoxetine after transdermal and oral administration to healthy cats

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

John Ciribassi, Andrew Luescher, Kirby S. Pasloske, Carol Robertson-Plouch, Alan Zimmerman, Liane Kaloostian-Whittymore

Revue : American Journal of Veterinary Research

Chicagoland Veterinary Behavior Consultants, 1042 Mountain Glen Way, Carol Stream, IL 60188. (Ciribassi); Behavior Clinic, Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Purdue University, West Lafayette, IN 47907. (Luescher); Elanco Animal Health Division, Eli Lilly and Company, 2001 W Main St, Greenfield, IN 46140. (Pasloske, Robertson-Plouch, Zimmerman, Kaloostian-Whittymore)


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. (Am J Vet Res 2003;64:994–998)

American Journal of Veterinary Research Aug 2003, Vol. 64, No. 8, Pages 994-998

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