Pharmacokinetics of Amitriptyline HCl and Its Metabolites in Healthy African Grey Parrots ( Psittacus erithacus ) and Cockatoos (Cacatua Species).

Amitriptyline, a tricyclic antidepressant, is used clinically to treat feather-destructive behavior in psittacine birds at a recommended dosage of 1-5 mg/kg PO q12-24h, which has been extrapolated from human medicine and based on anecdotal reports. The purpose of this pilot study was to describe the individual and population pharmacokinetic parameters of amitriptyline after a single oral dose at 1.5 mg/kg, 4.5 mg/kg, and 9 mg/kg in healthy African grey parrots ( Psittacus erithacus , n = 3) and cockatoos (Cacatua species, n = 3). Three birds received an initial 1.5 mg/kg oral dose, and blood samples were collected for 24 hours at fixed time intervals. Serum concentrations of amitriptyline and its metabolites were determined by polarized immunofluorescence. After determining the initial parameters and a 14-day washout period, 2 African grey parrots and 1 cockatoo received a single oral dose at 4.5 mg/kg, and 3 cockatoos and 1 African grey parrot received a single oral dose at 9 mg/kg. Concentrations reached the minimum therapeutic range reported in people (60 ng/mL) in 4 of 10 birds (4.5 and 9.0 mg/kg). Concentrations were within the toxic range in 1 African grey parrot (9 mg/kg), with regurgitation, ataxia, and dullness noted. Serum concentrations were nondetectable in 3 birds (1.5 and 4.5 mg/kg) and detectable but below the human therapeutic range in 3 birds (1.5 mg/kg and 9 mg/kg). Drug concentrations were continuing to increase at the end of the study (24 hours) in 1 bird. Elimination half-life varied from 1.6 to 91.2 hours. Population pharmacokinetics indicated significantly varied absorption, and elimination constants varied between species. Although amitriptyline appeared to be tolerated in most birds, disposition varies markedly among and within species, between the 2 genera, and within individual birds. The current recommended dosage of 1-5 mg/kg q12h in psittacine birds appears insufficient to achieve serum concentrations within the human therapeutic range and does not yield predictable concentrations. Results of this study suggest doses of up to 9 mg/kg may be necessary, although that dose may produce adverse events in some birds, and elimination half-life is sufficiently variable that dosing intervals are not predictable. Therapeutic drug monitoring combined with response to therapy is indicated to determine individual therapeutic ranges.

Comparison of Hematologic and Biochemical Test Results in Blood Samples Obtained by Jugular Venipuncture Versus Nail Clip in Moluccan Cockatoos (Cacatua moluccensis).

In birds, blood samples are often collected from the jugular, medial metatarsal, and basilic vein. Samples are sometimes collected by toe nail clip, but concerns to avoid drawing blood from the nail include pain after nail clips for blood collection, potential differences in complete blood count (CBC) results, and potential contamination with uric acid values. To compare differences in biochemical and hematologic values in blood samples obtained by jugular venipuncture versus toenail clip, blood samples were collected from Moluccan cockatoos (Cacatua moluccensis) (N = 23) and sent to a commercial laboratory for routine CBCs and serum biochemical analysis. Results showed good agreement between venipuncture and nail clip blood samples in red blood cell count, packed cell volume, heterophil count and percentage, lymphocyte count and percentage, aspartate aminotransferase, chloride, creatine phosphokinase, glucose, lactate dehydrogenase, total protein, and uric acid values. Constant bias was found in values of bile acids, cholesterol, and hemoglobin. Proportional bias toward higher values in the jugular sample were found in total white blood cell (WBC) count and inorganic phosphorus. Serum calcium plots revealed a proportional bias toward higher values in the toe nail blood when values were increased. Results suggest some differences in WBC count, bile acids, calcium, cholesterol, hemoglobin, and phosphorus values between blood samples collected by jugular venipuncture and samples collected by toe nail clip, but the differences are mostly minor and, with the possible exception of inorganic phosphorus and marginally elevated or very low WBC counts, are unlikely to affect the use or interpretation of the avian blood panel.

Assessment of plasma concentrations and potential adverse effects of doxycycline in cockatiels (Nymphicus hollandicus) fed a medicated pelleted diet.

Doxycycline hyclate was mixed with soybean oil and then added to a low-fat pelleted diet that contained approximately 2.4% fat, which produced a final diet that contained a calculated 6.4% fat and 300 mg doxycycline per kilogram of diet. The medicated diet was fed to 9 healthy adult cockatiels (Nymphicus hollandicus) for 47 days; a control group of 6 birds received the identical diet without doxycycline. Trough doxycycline plasma concentrations were measured 7 times during treatment and ranged from 0.98 to 3.83 microg/mL with an overall median of 2.09 microg/ mL. The birds were observed daily, weighed, and examined at least weekly, and selected plasma biochemical parameters were measured before treatment and at days 21 and 42. No adverse effects were noted, except one treatment bird became obese. This medicated diet may be suitable for treating spiral bacteria and Chlamydophila psittaci infections in cockatiels that will consume a pelleted diet.

Hematologic and plasma biochemical reference values for three species of black cockatoos (Calyptorhynchus species).

Black cockatoos in southwest Western Australia face population declines as a result of habitat loss and fragmentation, poaching, competition with other species, vehicle strikes, and shootings. In this study, hematologic and plasma biochemical reference values were determined for 3 endemic Western Australian black cockatoo species: Carnaby's cockatoo (Calyptorhynchus latirostris) (n = 34), Baudin's cockatoo (Calyptorhynchus baudinii) (n = 22), and forest red-tailed black cockatoo (Calyptorhynchus banksii naso) (n = 22). Significant sex-related differences were detected in Carnaby's cockatoos, and differences were also found among the 3 species. The forest red-tailed black cockatoos showed a markedly greater eosinophil count than did the 2 white-tailed species. Blood values from samples obtained by different collection methods differed significantly for Carnaby's cockatoos, which indicates that anesthesia may affect analyte values and that collection methods should remain consistent. The results of this study will be useful for clinically evaluating wild black cockatoos that are undergoing rehabilitation for release and will provide baseline data for future investigations of free-living black cockatoo health.

Effect of dietary omega-3 fatty acids on red blood cell lipid composition and plasma metabolites in the cockatiel, Nymphicus hollandicus.

Although dietary n-3 fatty acids have been extensively studied in poultry, they have not yet been prospectively investigated in psittacines, despite potential benefits for preventing and treating atherosclerosis, osteoarthritis, and other chronic disease processes. The objectives of this study were to investigate the incorporation of dietary n-3 fatty acids into red blood cells (RBC) and to determine the effects of supplementation of psittacine diets with fish or flax oil on plasma lipids and lipoproteins in the cockatiel. Adult cockatiels were fed a custom-formulated diet containing either 4% (wt/wt, as-fed) beef tallow (CON), 3% fish oil + 1% tallow (FSH), or 3.5% flax oil + 0.5% tallow (FLX; n = 20 per diet group). Baseline measurements were obtained for RBC fatty acid composition, triacylglycerides (TAG), and cholesterol. After 8 to 13 wk on the study diets, plasma chemistry profiles, lipoprotein density profiles, and RBC fatty acid composition were determined. At 8 wk, total plasma cholesterol was least in FSH birds (P < 0.05) and TAG concentrations were less in FSH birds than FLX birds (P < 0.05). Total n-3 fatty acids, docosahexaenoic acid, docosapentaenoic acid, and eicosapentaenoic acid were markedly greater in the RBC of FSH birds than FLX or CON birds (P < 0.05). Alpha linolenic acid was greatest in FLX (P < 0.05). Initial and final BW, and nonlipid plasma chemistry values did not differ among diet groups. No adverse effects of dietary supplementation of cockatiels with 3.5% flax oil or 3% fish oil were observed during the 13-wk feeding period. Although fish and flax oils provided similar total n-3 PUFA to the diets, fish oil caused greater reductions in cholesterol and TAG, and greater total RBC n-3 incorporation. Thus, dietary modification of psittacine diets with long chain n-3 PUFA from fish oil appears safe and may be beneficial to these long-lived companion birds.

Plasma concentrations of fluconazole after a single oral dose and administration in drinking water in cockatiels (Nymphicus hollandicus).

Candidiasis frequently affects the oropharynx, esophagus, and crop of juvenile birds with immature immune systems and adult birds that have received long-term antibiotic treatment. Fluconazole is used extensively in human medicine to treat mucosal and invasive candidiasis and has been used in birds; however, there have been few pharmacokinetic studies in avian species to guide safe and effective treatment. The purpose of the present study was to investigate the disposition of fluconazole in cockatiels (Nymphicus hollandicus) after single oral dose administration and to determine if therapeutic plasma concentrations could be safely achieved by providing medicated water. Twenty-eight cockatiels were placed into 7 groups and were orally administered a 10 mg/kg fluconazole suspension. Blood samples were collected from each group for plasma fluconazole assay at serial time points. Fluconazole-medicated drinking water was prepared daily and offered to 15 cockatiels at a concentration of 100 mg/L for 8 days. Blood was collected for plasma fluconazole assay at 2 time points on days 3 and 7. When using naive averaged data in the single-dose study, pharmacokinetic parameters were similar for both compartmental and noncompartmental analyses. The elimination half-life of fluconazole was 19.01 hours, maximum plasma concentration was 4.94 microg/mL, time until maximal concentration was 3.42 hours, and the area under the plasma concentration versus time curve (AUC) was 149.28 h x microg/mL. Computer-simulated trough and peak plasma concentrations at steady-state after multiple doses of fluconazole at 10 mg/kg every 24 hours, 10 mg/kg every 48 hours, and 5 mg/kg every 24 hours were approximately 4.1-8.5 microg/mL, 1.2-6.0 microg/mL, and 2.0-4.3 microg/mL, respectively. Mean +/- SD plasma fluconazole concentrations for the 100 mg/L medicated water study at 0800 and 1600 hours on day 3 were 3.69 +/- 1.22 microg/mL (range, 1.73-5.26 microg/mL) and 4.17 +/- 1.96 microg/mL (range, 3.58-7.49 microg/mL), respectively, and at 0800 and 1600 hours on day 7 were 4.78 +/- 0.91 microg/mL (range, 2.62-6.11 microg/mL) and 6.61 +/- 1.67 microg/mL (range, 3.76-8.78 microg/ mL), respectively. Treatment with fluconazole administered orally at a dosage of 5 mg/kg once daily or 10 mg/kg every 48 hours or fluconazole administered in the drinking water at a concentration of 100 mg/L is predicted to maintain plasma concentrations in most cockatiels that exceed the minimum inhibitory concentration of 90% or therapeutic AUC:MIC of most strains of Candida albicans (by using susceptibility data from humans). The compounded oral suspension was stable for 14 days when stored at 5 degrees C (41 degree sF) and protected from light.

Using a GnRH agonist to obtain an index of testosterone secretory capacity in the cockatiel (Nymphicus hollandicus) and sulphur-crested cockatoo (Cacatua galerita).

OBJECTIVE: Validation of a stimulation test for determining the steroidogenic capacity of the parrot testis. The major aim was to characterise testosterone secretion after injection of a gonadotropin-releasing hormone agonist (GnRHa), then use the test to investigate seasonal reproduction in the male cockatiel. PROCEDURE: A synthetic GnRHa (buserelin; 8.0 microg of peptide/kg bodyweight) was injected IM into male cockatiels (n = 7) and sulphur-crested cockatoos (n = 3) and serial blood samples collected at 0, 30, 60, 90 and 120 min after administration. Once validated, the technique was subsequently used to examine seasonal changes (23 months) in the testosterone profile of a captive cockatiel population. RESULTS: Injection of buserelin resulted in a significant increase in the testosterone concentration of cockatiel plasma, with maximal concentrations occurring at approximately 60 (1.33 +/- 0.08 ng/mL) to 90 min (1.22 +/- 0.08 ng/mL) after injection. Although no clear pattern of seasonal variation in testosterone secretion was detected in cockatiel plasma, samples taken 60 and 90 min after administration showed a significant increase in all seasons. Injection of buserelin in the sulphur-crested cockatoo also resulted in increased testosterone secretion, with maximal concentrations obtained after 90 min. CONCLUSION: Buserelin can be used to obtain a reliable index of the prevailing testosterone capacity of the cockatiel and cockatoo testis. With further studies, this test may be incorporated into clinical assessment of reproductive status.

Health and nutritional status of wild Australian psittacine birds: an evaluation of plasma and hepatic mineral levels, plasma biochemical values, and fecal microflora.

To evaluate the health and nutritional status of 3 wild Australian psittacine species, plasma and hepatic mineral concentrations and plasma biochemical values were measured in wild-caught galahs (Eolophus roseicapilla), long-billed corellas (Cacatua tenuirostris), and sulphur-crested cockatoos (Cacatua galerita). No correlations were found between hepatic and plasma mineral levels. Mean plasma calcium (1.79 mmol/L [7.16 mg/dL]) and sodium (103 mmol/ L [103 mEq/L]) concentrations were lower, whereas mean total phosphorus (6.53 mmol/L [20.22 mg/dL]) and potassium (8.87 mmol/L [8.87 mEq/L]) concentrations were higher than values for captive counterparts. Plasma iron levels were higher than those reported for captive counterparts, with evidence of interspecific (sulphur-crested cockatoos, 109 micromol/L [609 microg/dL]; corellas, 57 micromol/L [318 microg/dL]; galahs, 90 micromol/L [503 microg/dL]) and temporal variation (galahs: May, 107 micromol/L [598 microg/dL]; July, 59 micromol/L [330 microg/dL]). Hepatic iron concentrations were as high as 1030 mg/kg. Interspecific variation was minimal in mean plasma selenium (11.8 micromol/L [929 microg/L]) and zinc (31.2 micromol/L [204 microg/dL]) concentrations. Plasma biochemical values varied significantly from reported reference ranges. Ranges for total protein, albumin, and bile acid concentrations were lower, whereas uric acid, glutamate dehydrogenase, amylase, and cholesterol concentrations were higher than those previously reported for these species, and interspecific variation was evident. Variation in measures of mineral status or plasma biochemical values between males and females were negligible. An evaluation of fecal microflora showed a distinct absence of gram-negative bacteria or budding yeast. Results of this study show that analyte values used to determine health and nutritional status of wild birds differ from those published for captive counterparts. Although analyte values appear to vary minimally by sex, distinct taxonomic and some temporal differences exist in values from wild birds of these 3 species.