Objective—To determine bioavailability, pharmacokinetics,
and safety for transdermal (TD) and oral
administration of fluoxetine hydrochloride to healthy
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,
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)
Objective—To evaluate efficacy of fluoxetine hydrochloride for treatment of compulsive disorders in dogs.
Design—Randomized, controlled clinical trial.
Animals—63 dogs with compulsive disorders.
Procedures—The diagnosis was confirmed on the basis of analysis of videotapes of the dogs' behavior by 3 veterinary behaviorists, results of physical examination and clinicopathologic testing, and, when necessary, telephone interviews with owners. Dogs were randomly assigned to treatment with fluoxetine (1 to 2 mg/kg [0.45 to 0.9 mg/lb], PO, q 24 h) or a placebo. Owners did not receive any advice regarding behavioral or environmental modifications. Severity of episodes was measured through telephone interviews every 2 weeks and on the basis of a daily diary kept by each owner.
Results—42 days after the initiation of treatment, the proportion of dogs with a decrease in severity of the compulsive disorder, as reported by the owners, was significantly higher for dogs treated with fluoxetine than for control dogs, and dogs treated with fluoxetine were significantly more likely (odds ratio, 8.7) to have a decrease in severity of the compulsive disorder. However, mean number and duration of compulsive episodes, as determined from daily diary entries, did not differ significantly between groups. The most common adverse effects were decreased appetite and mild lethargy.
Conclusions and Clinical Relevance—Results suggested that fluoxetine may be efficacious in the treatment of compulsive disorders in dogs, although results were equivocal. The present study did not examine whether fluoxetine was more efficacious than or synergistic with behavioral and environment modifications.