Abstract
Itraconazole, an azole anti-fungal agent, has been widely used in avian medicine, primarily as a treatment for aspergillosis. Oral administration of itraconazole to birds has proved problematic as the most economical formulation, SporanoxR (100 mg capsules, Janssen Cilag Pty. Ltd., Lane Cove, NSW, Australia) provides too large a dose for most avian patients (recommended dosage is 100 mg/kg SID or BID). Each capsule contains approximately 260 small inert plastic beads spray coated with a thin layer of itraconazole. Itraconazole therapy has previously involved dosing birds according to individual body weight. This is especially difficult in birds of less than 100 g. In addition, individual dosing often necessitates frequent handling of patients. This study investigated the use of itraconazole-medicated seed in a group of Gouldian finches (Chloebia gouldiae), average body weight 16 g.
A group of Gouldian finches housed in a heated outdoor aviary at Melbourne Zoo developed multiple disease problems. Chronic feather loss of the head and neck, associated with hyperkeratosis of skin, beak and feet was seen in many individuals. Histopathology suggested dermatomycosis although fungal elements have not been cultured. Previous studies found that itraconazole beads added to seed achieved above therapeutic levels in plasma of Gouldian finches.1
Itraconazole-medicated seed (20 or 100 mg itraconazole per 100 g seed) was offered to Gouldian finches ad lib for extended periods of time. SporanoxR microbeads (approximately 0.39 mg per bead) were mixed with seed and a little vegetable oil. The mix was offered fresh daily.
Blood was collected from the jugular vein of anesthetized finches and serum was submitted for itraconazole assay.2 Feathers and plucked skin were collected separately from recently euthanatized finches and submitted for itraconazole assay.3 Full postmortem examination was conducted on each dead bird and a range of tissues submitted for histopathologic examination.
Serum from finches fed 100 mg itraconazole per 100 g seed for more than 40 days was pooled to provide one sample, with an itraconazole level of 7040 nmol/L. Therapeutic efficacy is reported to be achieved at levels greater than 350 nmol/L (Janssen Cilag, personal communication).
Serum levels in finches fed 20 mg itraconazole per 100 g seed for more than 80 days averaged 1278 nmol/l (range: 293–2377 nmol/L; n=7).
Skin itraconazole levels in finches fed 20 mg itraconazole per 100 g seed for more than 40 days averaged 1077 pmol/g (range: 526–1945 pmol/g; n=5).
Feather itraconazole levels in finches fed 20 mg itraconazole per 100 g seed for more than 40 days were all below 5 pmol/g (n=5).
Skin itraconazole levels in finches fed 20 mg itraconazole per 100 g seed for more than 100 days averaged 1394 pmol/g (range: 1163–1624 pmol/g; n=2).
Feather itraconazole levels in finches fed 20 mg itraconazole per 100 g seed for more than 100 days averaged 444 pmol/g (range: 402–486 pmol/g; n=2).
Histologic examination of postmortem tissues did not show evidence of pathology attributable to itraconazole toxicity.
Feather regrowth was noted in most, but not all finches following prolonged itraconazole therapy. Histopathology indicated birds with unresolved feather loss were suffering from chronic hyperkeratosis and follicular atrophy. Fungal elements were not detected in histology, or by culture in finches following 100 days of itraconazole treatment.
These studies indicated that medication of seed with SporanoxR microbeads is an effective method of administration of itraconazole to groups or individual seed-eating birds. Serum levels in birds fed itraconazole at 20 mg per 100 g seed averaged well above that reported to be required for therapeutic efficacy. Skin levels were equivalent to serum levels indicating itraconazole should be effective in azole-susceptible avian dermatomycoses. There was significant increase in feather itraconazole levels over time indicating itraconazole may take many months to reach therapeutic levels in feathers.
Literature Cited
1. Schultz DJ, Spanner AM. Neonatal mortalities in Gouldian finches at Adelaide Zoological Gardens. In: Proceedings of the Association of Avian Veterinarians (Australasian Section) Annual Conference. 1995:91–98.
2. Badcock NR. Microscale method for itraconazole in plasma by reverse phase, high performance liquid chromatography. J Chromatog. 1990;525:478–483.
3. Badcock NR, Davies A. Assay for itraconazole in nail clippings by reversed phase high performance liquid chromatography. Ann Clin Biochem. 1990;27:506–508.