Aspergillosis is a commonly reported fungal disease that results in illness and death in avian species.1–6 Species reportedly at increased risk of infection include raptors, waterfowl, poultry, and psittacine birds, specifically Amazon parrots and African grey parrots (Psittacus erithacus).1,4 Successful treatment of aspergillosis often requires long-term, systemic treatment with antifungals delivered IV, orally, topically, or via nebulization.3,4 Drugs commonly used include itraconazole, clotrimazole, fluconazole, voriconazole, and amphotericin B, but adverse effects seen with these drugs, including liver and kidney damage, can sometimes preclude their use in some species and animals. In addition, treatment failures have been reported with the use of itraconazole and voriconazole for infections caused by certain strains of Aspergillus fumigatus, the most commonly isolated Aspergillus organism.7
Terbinafine hydrochloride, an allylamine antifungal commercially available in topical and oral formulations, provides primarily fungicidal action with a broad range of in vitro activity.8 Terbinafine prevents fungal biosynthesis of ergosterol, necessary for cell membrane synthesis, via the inhibition of squalene expoxidase.5,6,9 Historically, terbinafine has been used for the treatment of dermatophytosis, but it has been found that terbinafine is useful in the treatment of refractory and systemic fungal infections, particularly aspergillosis.10,11 An increase in Cmax has been detected in humans when terbinafine is administered with food.12 Oral administration of terbinafine is generally tolerated better than is other available antifungal drugs, but adverse effects, including mild to moderate gastrointestinal tract discomfort, rash or urticaria, and malaise, can develop.10
Currently, terbinafine is not licensed for use in veterinary medicine but is routinely used in an extralabel manner to treat fungal infections, especially dermatophytosis in small animal medicine.13 Pharmacokinetics and dose recommendations for terbinafine have been reported for cats,13 dogs,14,15 horses,15 red-tailed hawks (Buteo jamaicensis),5 and penguins (Spheniscus demersus).6 The recommended dose of terbinafine is 22 mg/kg/d and 15 mg/kg/d for red-tailed hawks5 and penguins,6 respectively. We are not aware of any published doses derived from pharmacokinetic or pharmacodynamic studies for psittacine species such as Amazon parrots. Oral administration of doses of 15 mg/kg reportedly have been used clinically for the treatment of aspergillosis in psittacine birds with favorable results,16 but preliminary pharmacokinetic trials with that dose failed to yield measurable plasma concentrations in African grey parrots.17
Comparative in vitro testing has revealed that terbinafine is more effective against Aspergillus spp than are other drugs (including azole antifungal drugs and amphotericin B) commonly used to treat diseases attributable to those organisms.4,16,18 The elimination of terbinafine in humans requires < 5% of the total cytochrome P450 capacity of the liver, which may minimize adverse effects when terbinafine is used alone or in combination with other antifungal drugs. Terbinafine also has a better safety profile than the azole antifungals and amphotericin B, with few adverse effects reported in human and veterinary medicine.5,6,8,9
The purpose of the study reported here was to determine the pharmacokinetics of terbinafine after oral administration to Hispaniolan Amazon parrots (Amazona ventralis). These parrots were selected for use in the study because of their popularity as companion animals and the high frequency of aspergillosis in Amazon parrots, compared with the frequency of the disease in other species of psittacine birds.4 The size of the parrots also enabled us to safely collect an adequate volume of blood from each bird at all time points.
Area under the plasma concentration-time curve from time 0 to infinity
Maximum plasma concentration
Minimum inhibitory concentration
Time to maximum plasma concentration
Lafeber's Premium Daily Diet, Lafeber Co, Cornell, Ill.
Exact hand feeding formula, Kaytee Products Inc, Chilton, Wis.
Ora-Plus oral suspending vehicle (50 mL), Paddock, Minneapolis, Minn.
Ora-Sweet syrup (100 mL), Paddock Laboratories Inc, Minneapolis, Minn.
2695 separations module, Waters Corp, Milford, Mass.
2487 absorbance detector, Waters Corp, Milford, Mass.
Empower software, Waters Corp, Milford, Mass.
Symmetry Shield, Waters Corp, Milford, Mass.
WinNonlin, version 5.2, Pharsight Corp, Mountain View, Calif.
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