Systemic Absorption of Amitriptyline and Buspirone after Oral and Transdermal Administration to Healthy Cats

Abstract

A prospective study was performed to determine the relative availability of buspirone and amitriptyline after oral and transdermal routes of administration in 6 adult cats. For topical administration, drugs were compounded in a transdermal organogel containing pluronic and lecithin (PLO). Using a crossover design, each cat received a single dose of amitriptyline (5 mg) and buspirone (2.5 mg) by the transdermal and oral route of administration with at least a 2-week washout interval between drug treatments. Blood samples were obtained at 0, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours after drug administration for determination of plasma drug concentrations. Plasma concentrations of immunoreactive amitriptyline and buspirone were determined using commercial enzymelinked immunosorbent assay (ELISA) tests. Systemic absorption of amitriptyline and buspirone administered by the transdermal route was poor compared with the oral route of administration. Until supporting pharmacokinetic data are available, veterinarians and cat owners should not rely on the transdermal route of administration for treating cats with amitriptyline or buspirone.Key Words: Cat; Pharmacokinetics. Behavior problems are among the most common reasons pet owners surrender otherwise healthy pets, 1 and urine spraying is one of the most common feline behavioral disorders. Urine spraying is reported to be a sporadic problem in up to 30% of all cats and a habitual problem in 12% of male cats and 5% of female cats.2 Pharmacological therapy for urine spraying in cats is often effective, with 55-75% of cats showing marked reduction or complete cessation of the undesired behavior.2 Buspirone, a nonspecific anxiolytic, which may act as a partial serotonin agonist, 3 and amitriptyline, a tricyclic antidepressant, 4 have been recommended for treatment of behavior problems, including urine spraying, in cats. 5-9Chronic administration of any medication to cats can be problematic for several reasons. Relatively few drugs have received Food and Drug Administration (FDA) approval for use in cats, and drug formulations appropriate for use in cats (ie, small tablet or capsule size and strength, palatable liquid formulations) are limited. Cats may resist oral drug administration, and even the most docile of cats may resort to the use of claws and teeth to avoid being pilled on a daily basis. Liquid medications also are difficult to administer because the presence of an unpleasant-tasting substance in a cat's mouth often induces profuse salivation. In response, veterinary compounding pharmacies recently have advertised transdermal gels as an alternative route of drug administration for cats. Transdermal formulations of both buspirone and amitriptyline are routinely advertised by veterinary compounding pharmacies. However, transdermal absorption of buspirone and amitriptyline has not been evaluated in cats. The purpose of this study was to test the hypothesis that the systemic absorption of transdermally administered buspirone and amitriptyline is similar to systemic absorp...

The Efficacy and Safety of a Novel Lipophilic Formulation of Methimazole for the Once Daily Transdermal Treatment of Cats with Hyperthyroidism

“…Because of this, many compounding pharmacies have started formulating drugs into gels, which are applied to the inner side of the cat's ear and are thought to be absorbed through the skin for systemic action. [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] Not all drugs are suitable for transdermal penetration and only a few drugs have been studied in cats to determine whether they reach therapeutic concentrations after absorption by this route. [21][22][23]26,27,30,31 There are several factors that affect the transdermal delivery of drugs.…”

Drug compounding for veterinary patients

“…31,32 In the most recent study, 31 the authors showed that transdermal methimazole was not as effective as oral methimazole for treating hyperthyroid cats, but it may be an option for some cats that are difficult to medicate orally. Amitriptyline and buspirone administered transdermally to cats 33 showed negligible transdermal absorption. When dexamethasone was topically administered in PLO, there was negligible absorption in cats.…”

Preparation, characterization, and in vitro release of new transdermal methimazole as alternative to oral delivery

“…In veterinary medicine, there are studies on transdermal absorption of different active substances such as fluoxetine (Ciribassi et al 2003), fentanyl, morphine (Krotscheck et al 2004), dexamethasone (Willis-Goulet et al 2003), buspirone, amitryptylene (Mealey et al 2004), glypizide (Bennett et al 2005), and methimazole (Hoffmann et al 2003).…”