Cats commonly develop allergies affecting the skin, respiratory system, and gastrointestinal tract. Clinical signs of allergic disease can range from mild and irritating (eg, pruritus in atopic dermatitis) to severe and life-threatening (eg, bronchoconstriction in asthma). Although glucocorticoids are effective for the treatment of animals with allergic disease, high-dose or long-term administration has been associated with adverse drug events. Additionally, glucocorticoids may be relatively contraindicated in cats with diabetes mellitus, infectious disease, and certain types of heart disease; therefore, alternative treatments should be explored. In humans, second-generation antihistamines, such as cetirizine, have provided relief to patients that had various allergic symptoms with fewer adverse effects, compared with results for patients administered first-generation antihistamines.1
Cetirizine, the active metabolite of hydroxyzine, is a potent second-generation H1 receptor antagonist.2,3 It is considered a second-generation antihistamine because, in contrast to earlier antihistamines, it does not cause sedation in people. Hydroxyzine, the parent drug of cetirizine, results in considerably more sedative effects. In dogs, practically all of an administered dose of hydroxyzine is converted to the active drug cetirizine after IV or oral administration.a In those same dogs, the pharmacodynamic effects (suppression of histamine) were attributed to cetirizine concentrations, rather than to the effects of hydroxyzine.a Even though cetirizine and hydroxyzine have similar structural and H1 receptor binding characteristics, concentrations in the brain differ.3,4 Because cetirizine is a substrate for the efflux protein (ie, p-glycoprotein), it does not accumulate in the CNS to cause sedation.3 Even though histamine is only one of many components in the allergic cascade, antihistamine block of the H1 receptor has been used successfully to minimize the clinical signs of many allergic diseases.5 After histamine is released, it binds to the H1 receptor, inflammatory cells are recruited, vascular permeability and plasma extravasation increase, and smooth muscle constricts, which ultimately lead to clinical signs of an allergy.5,6
Instead of blocking histamine receptors, antihistamines act as inverse agonists, which stabilize the inactive form of the H1 receptor and shift activity toward an inactive state.1 Antihistamines have been advocated for use in humans with urticaria, atopic dermatitis, allergic rhinitis, and mild asthma.7,8 The improvement in clinical signs can be attributed to antihistamine effects and anti-inflammatory effects independent of blocking of the H1 receptor.5,9 Additional anti-inflammatory effects may include attenuation of inflammatory cell migration, inhibition of inflammatory mediator release, and inhibition of expression of adhesion molecules.1,4,10,11 Because of the success of this drug in human medicine, cetirizine may be a viable alternative to glucocorticoid use in cats with allergic disease.
Although there is anecdotal information about the use of cetirizine in cats,12 the authors are not aware of published pharmacokinetic studies of this drug in cats, and an appropriate dose for oral administration has not been established by the use of scientific methods. Before clinical studies can be evaluated in cats, the pharmacokinetics (particularly characteristics of oral absorption) require investigation. There is no formulation available for IV administration; therefore, the study reported here was limited to oral administration. Several methods have been developed for detection of cetirizine in human plasma, including gas chromatography, thinlayer chromatography with radiolabeled methods, and HPLC with UV and mass spectrometric detection.13,14 The HPLC method is rapid, allows multiple samples to be assayed in a short amount of time, uses an extraction technique that can be performed in most laboratory settings, and allows detection of low concentrations of cetirizine in plasma.14 The objective of the study reported here was to develop and validate an HPLC method of measuring cetirizine in feline plasma and to characterize the pharmacokinetic characteristics of cetirizine in cats after oral administration of a single dose. Plasma protein binding is high (93%) in humans, and only the unbound fraction is active. Therefore, an additional objective was to determine the protein binding of cetirizine in feline plasma. We hypothesized that in healthy cats, a dose of 5 mg of cetirizine administered orally once daily would yield effective therapeutic plasma concentrations (ie, concentrations in a range reported to be effective for humans).
Histamine type 1
High-pressure liquid chromatography
Fraction of drug absorbed
First-order rate constant for oral absorption
Apparent volume of distribution
First-order rate constant for drug elimination
Area under the plasma concentration-versus-time curve
Time until peak plasma concentration
Peak plasma concentration
Coefficient of variation
Bizikova P, Papich MG, Olivry T. Pharmacokinetics and pharmacodynamics of hydroxyzine and cetirizine after hydroxyzine administration to healthy dogs (abstr) Vet Dermatol 2008;19;106.
Zyrtec cetirizine dihydrochloride tablets, Pfizer Inc, New York, NY.
Provided by Dr. Peggy Dillender, Pfizer Animal Health, New York, NY.
Agilent 1100 Series quaternary solvent delivery system, Agilent Technologies, Wilmington, Del.
Agilent 1100 Series autosampler, Agilent Technologies, Wilmington, Del.
Agilent 1100 Series variable wavelength detector, Agilent Technologies, Wilmington, Del.
Agilent 1100 Series Chemstation software, Agilent Technologies, Wilmington, Del.
Zorbax Rx-C8 high-performance liquid chromatography column, 4.6 × 150 mm, 5 μm, Agilent Technologies Inc, Wilmington, Del.
SPEC-C18AR solid-phase extraction cartridges, 3 mL, Varian, Palo Alto, Calif.
WinNonlin, version 5.0.1, Pharsight Corp, Mountain View, Calif.
Centrifree Micropartition System, Amicon, Beverly, Mass.
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