High-concentration buprenorphine exceeds target plasma concentrations for extended periods following subcutaneous administration in American flamingos (Phoenicopterus ruber).

OBJECTIVE: To determine the pharmacokinetic parameters of a high-concentration buprenorphine formulation after a single SC dose in American flamingos (Phoenicopterus ruber). ANIMALS: 6 healthy adult American flamingos (3 males and 3 females). METHODS: A single dose of high-concentration buprenorphine (1.8 mg/kg) was administered SC to all birds. Blood samples were collected at 0.25, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 96 hours after drug administration between October 14 and October 18, 2022. Plasma buprenorphine concentrations were determined by liquid chromatography-tandem mass spectrometry and a noncompartmental analysis was used to determine pharmacokinetic parameters. RESULTS: Mean ± SD peak plasma drug concentration (Cmax) was 195.1 ± 187.4 ng/mL, the mean time to peak plasma concentration (Tmax) was 0.32 ± 0.31 hours, the mean area under the concentration-vs-time curve from time 0 to the last measured concentration (AUC0-last) was 881.4 ± 205.4 ng/mL, and mean terminal half-life (t1/2) was 12.6 ± 3.86 hours. Mean plasma buprenorphine concentrations were >1 ng/mL for at least 48 hours after drug administration. No clinically significant adverse effects were observed. CLINICAL RELEVANCE: High-concentration buprenorphine dosed at 1.8 mg/kg SC in American flamingos rapidly exceeded plasma drug concentrations reported to have analgesic effects in other avian species and maintained these levels for extended periods. Sedative effects were similar to those reported for other species. Additional studies are needed to evaluate the clinical efficacy of high-concentration buprenorphine at this dose in American flamingos.

Pharmacokinetics of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVES: To characterize the pharmacokinetics of a single oral dose (6 mg/kg) of mavacoxib in New Zealand White rabbits (Oryctolagus cuniculus) and to characterize any clinicopathologic effects with this medication and dose. ANIMALS: Six healthy, 4-month-old New Zealand White rabbits (3 male, 3 female). PROCEDURES: Before drug administration, clinicopathologic samples were collected for baseline data (CBC, serum biochemical analyses, and urinalysis including urine protein-to-creatinine ratio). All 6 rabbits received a single oral dose (6 mg/kg) of mavacoxib. Clinicopathologic samples were collected at set time intervals to compare with the baseline. Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using non-compartmental methods. RESULTS: After a single oral dose, the maximum plasma concentration (Cmax; mean, range) was 854 (713-1040) ng/mL, the time to Cmax (tmax) was 0.36 (0.17-0.50) days, the area under the curve from 0 to the last measured time point (AUC0-last) was 2000 (1765-2307) days*ng/mL, the terminal half-life (t1/2) was 1.63 (1.30-2.26) days, and the terminal rate constant (λz) was 0.42 (0.31-0.53) days. All results for CBCs, serum biochemical analyses, urinalyses, and urine protein-to-creatinine ratios remained within published normal reference intervals. CLINICAL RELEVANCE: This study determined that plasma concentrations reached target levels of 400 ng/mL for 48 hours in 3/6 rabbits at 6 mg/kg PO. In the remaining 3/6 rabbits, the plasma concentrations were 343-389 ng/mL at 48 hours, which is below the target concentration. Further research is needed to make a dosing recommendation, including a pharmacodynamic study and investigating pharmacokinetics at different doses and multiple doses.

Feeding decreases the oral bioavailability of cannabidiol and cannabidiolic acid in hemp oil in New Zealand White rabbits (Oryctolagus cuniculus).

OBJECTIVE: To determine the pharmacokinetics of a solution containing cannabidiol (CBD) and cannabidiolic acid (CBDA), administered orally in 2 single-dose studies (with and without food), in the domestic rabbit (Oryctolagus cuniculus). ANIMALS: 6 healthy New Zealand White rabbits. PROCEDURES: In phase 1, 6 rabbits were administered 15 mg/kg CBD with 16.4 mg/kg CBDA orally in hemp oil. In phase 2, 6 rabbits were administered the same dose orally in hemp oil followed by a food slurry. Blood samples were collected for 24 hours to determine the pharmacokinetics of CBD and CBDA. Quantification of plasma CBD and CBDA concentrations was determined using a validated liquid chromatography-mass spectrometry (LC-MS) assay. Pharmacokinetics were determined using noncompartmental analysis. RESULTS: For CBD, the area under the curve extrapolated to infinity (AUC)0-∞ was 179.8 and 102 hours X ng/mL, the maximum plasma concentration (Cmax) was 30.4 and 15 ng/mL, the time to Cmax (tmax) was 3.78 and 3.25 hours, and the terminal half-life (t1/2λ) was 7.12 and 3.8 hours in phase 1 and phase 2, respectively. For CBDA, the AUC0-∞ was 12,286 and 6,176 hours X ng/mL, Cmax was 2,573 and 1,196 ng/mL, tmax was 1.07 and 1.12 hours, and t1/2λ was 3.26 and 3.49 hours in phase 1 and phase 2, respectively. Adverse effects were not observed in any rabbit. CLINICAL RELEVANCE: CBD and CBDA reached a greater Cmax and had a longer t1/2λ in phase 1 (without food) compared with phase 2 (with food). CBDA reached a greater Cmax but had a shorter t1/2λ than CBD both in phase 1 and phase 2. These data may be useful in determining appropriate dosing of cannabinoids in the domestic rabbit.

Pharmacokinetics of Cannabidiol in the Hispaniolan Amazon Parrot (Amazona ventralis).

The purpose of this study was to determine the pharmacokinetics of cannabidiol (CBD), a potential treatment option that may alleviate pain in companion animals and humans, in the Hispaniolan Amazon parrot (Amazona ventralis). A pilot study administered a single oral dose of CBD in hemp oil at 10 mg/kg to 2 birds and 20 mg/kg to 2 birds. Because the maximum serum concentrations (Cmax) for these doses were 5.5 and 13 ng/mL, respectively, and the serum half-life was 2 hours for both groups, the doses were considered too low for clinical use in this species. Therefore, a study was designed in which 14 healthy 12-14-year-old parrots of both sexes and weighing 0.24-0.35 kg (mean, 0.28 kg) were enrolled. Seven birds were administered 60 mg/kg CBD PO, and 7 birds were administered 120 mg/kg CBD PO. Blood samples were obtained at time 0, and at 0.5, 1, 2, 3, 4, 6, and 10 hours posttreatment in a balanced incomplete block design. Quantification of plasma CBD concentrations was determined by use of a validated liquid chromatography-mass spectrometry assay. Pharmacokinetic parameters were determined by noncompartmental analysis. The areas under the curve (h·ng/mL) were 518 and 1863, Cmax (ng/ mL) were 213 and 562, and times to achieve Cmax (hours) were 0.5 and 4 for the 60 and 120 mg/kg doses, respectively. The serum half-life could not be determined in the 60 mg/kg treatment, but was 1.28 hours at 120 mg/kg. Adverse effects were not observed in any bird. The highly variable results and short half-life of the drug in Hispaniolan Amazon parrots, even at high doses, suggests that this drug formulation was inconsistent in achieving targeted concentrations as reported in other animal species.

Pilot Study of a Single Dose of Orally Administered Tapentadol Suspension in Hispaniolan Amazon Parrots (Amazona ventralis).

Tapentadol is an analgesic agent that acts as both a µ-opioid receptor agonist and a norepinephrine reuptake inhibitor. It is a common therapeutic agent in human medicine for management of acute and chronic pain, and it is currently being investigated for use in veterinary medicine. Tapentadol was evaluated in Hispaniolan Amazon parrots (Amazona ventralis) because there is only 1 other oral opioid-like analgesic agent, tramadol, which has been evaluated in an avian species. The effectiveness of tramadol after administration to a patient involves a complex physiologic metabolism and has been found to have variable pharmacokinetics between species. Because of the lack of active metabolites from tapentadol, less interspecific variation was expected. Seven Hispaniolan Amazon parrots were used to evaluate the pharmacokinetics of tapentadol after a single 30 mg/kg PO administration of a compounded 5 mg/mL tapentadol suspension. Blood samples were collected before (time 0) and 0.25, 0.5, 0.75, 1, 1.5, 3, and 6 hours after administration, following a balanced, incomplete-block design. Plasma tapentadol concentrations were measured by high-pressure liquid chromatography with mass spectrometry. Results revealed detectable plasma concentrations in only 2 of 7 birds (29%), and the bird with the highest plasma levels had a peak concentration (Cmax) of 143 ng/mL and a half-life (T 1/2) of 24.8 minutes. The variable plasma concentrations and short half-life of this drug in Hispaniolan Amazon parrots suggests that this drug would be of limited clinical use in this species; however, it is possible that this drug will be more bioavailable in other avian species.

PHARMACOKINETICS OF ORAL MAVACOXIB IN CARIBBEAN FLAMINGOS (PHOENICOPTERUS RUBER RUBER).

Mavacoxib is a selective cyclooxygenase-2 nonsteroidal anti-inflammatory drug that has been used for management of osteoarthritis and other inflammatory conditions in dogs. The main advantage of mavacoxib over other nonsteroidal anti-inflammatory drugs is its longer plasma half-life, leading to decreased dosing frequency. This study determined the pharmacokinetics of mavacoxib in Caribbean flamingos (Phoenicopterus ruber ruber) after a single-dose oral administration of 6 mg/kg (n = 6). Plasma mavacoxib concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using noncompartmental methods. Mean peak plasma concentration (Cmax) was (mean; range) 2.97 (2.19--4.06) µg/ml; mean time to peak plasma concentration (Tmax) was 18.68 (4.00-48.00) hr; mean area under the curve (AUC) was 455 (292-637) hr * µg/ml; and mean terminal half-life (T1/2) was 74.47 (49.57-161.43) hr. Based on the results of this study, mavacoxib dosed at 6 mg/kg orally in Caribbean flamingos reaches plasma concentrations above the therapeutic concentration established for dogs, but further studies are needed to determine appropriate dosing recommendations in flamingos.

Clinical, morphological, and molecular characterization of an undetermined Babesia species in a maned wolf (Chrysocyon brachyurus).

A possible novel Babesia species infection of a maned wolf (Chrysocyon brachyurus) was first reported in 2012. The current case details a confirmed report of a maned wolf with infection by an undetermined species of Babesia. As the mortality and morbidity of babesiosis is high, this may become a significant concern to captive maned wolves, which are considered a near-threatened species by the World Association of Zoos and Aquariums. The aim of this study is to report the clinical, morphological and molecular characterization of this Babesia species. A 2.5-year-old, intact female maned wolf was found laterally recumbent with pale mucous membranes and jaundice the morning of presentation. Hematological and serum biochemical data were consistent with babesiosis and showed a regenerative severe anemia, leukocytosis, thrombocytopenia, hyperbilirubinemia, azotemia, increased creatine phosphokinase and increase alanine aminotransferase. On blood film review, inclusion bodies were seen in the red blood cells with cytomorphological features that were most consistent with a small form Babesia species. A blood sample was sent for polymerase chain reaction (PCR) testing and multi-locus sequence analyses. These findings suggested a unique Babesia species that is most closely related to a Babesia species (Babesia sp. AJB-2006) that has been found to infect raccoons (Procyon lotor) in North America. Although the cytomorphological features of the piroplasms and the clinical presentation were similar in both the current and 2012 case, when comparing the 18S melt curve temperature of the two Babesia isolates, the peak temperature was different. Unfortunately, genetic material from the 2012 case was not available so comparison of multi-locus gene sequences could not be performed, excluding the possibility to definitively state if the Babesia spp. from both cases were distinct from each other. The maned wolf was treated with a whole blood transfusion, dexamethazone (0.28 mg/kg IM), azithromycin (10 mg/kg in NaCl SC), atavaquone (1.5 cc PO), and 2 imidocarb (6.6 mg/kg IM) injections, and clinically improved. These findings demonstrate the need to further characterize the molecular and epidemiological differences of the Babesia species in this case report and the Babesia species known to infect raccoons.

Surgical Management of an Intrathoracic Branchial Cyst in a Yellow-crested Cockatoo (Cacatua sulphurea).

A 40-year-old, female lesser crested cockatoo (Cacatua sulphurea) was presented with a complaint of hyporexia and sudden onset of sneezing and wheezing. Physical examination revealed mild stertorous inhalation, and the apex of the heart was palpable caudoventral to the distal tip of the sternum. Projection radiographic images showed a soft tissue mass displacing the heart and the thoracic portion of the trachea. A subsequent computed tomography series revealed a single, large, and predominantly encapsulated soft-tissue mass. The mass was contained within the cranial thoracic region and occupied most of the anatomic location of the thoracic portion of the clavicular air sac, extending around a portion of the trachea. A surgical exploratory procedure was performed, with a thoracic inlet thoracotomy, and the mass was found to be cystic and deeply attached to surrounding tissues at its caudal-most aspect. Complete excision was not possible, and the mass was drained and an incomplete resection was accomplished with approximately one-half of the cystic structure removed and submitted for histopathology. The mass was found to be benign, epithelial-lined, dense, fibrous connective tissue that would be consistent with a branchial cyst.

PHARMACOKINETICS OF ORAL GABAPENTIN IN CARIBBEAN FLAMINGOS ( PHOENICOPTERUS RUBER RUBER).

Gabapentin is a first-line treatment for neuropathic pain and adjunct anticonvulsant medication in humans and other species. Gabapentin may have advantages over other analgesics because of its broad therapeutic range with limited adverse effects and wide availability as an oral formulation. This study determined the pharmacokinetics of gabapentin in Caribbean flamingos ( Phoenicopterus ruber ruber) after a single-dose oral administration of either 15 mg/kg ( n = 6) or 25 mg/kg ( n = 6). Plasma gabapentin concentrations were determined using liquid chromatography with mass spectrometry, and pharmacokinetic analysis was performed using noncompartmental methods. Respectively for the 15 mg/kg and 25 mg/kg dose, mean peak plasma concentration ( Cmax) was (mean ± pseudo SD) 13.23 ± 1.47 and 24.48 ± 5.81 µg/ml; mean time to peak plasma concentration ( Tmax) was 0.50 ± 0.24 and 0.56 ± 0.28 hr; mean area under the curve (AUC) was 76.0 ± 26.3 and 114.7 ± 27.5 hr·µg/ml; and mean terminal half-life ( T1/2) was 3.39 ± 0.90 and 4.46 ± 1.12 hr. Based on the results of this study, gabapentin dosed at 25 mg/kg orally in most Caribbean flamingos is likely to maintain plasma concentrations above the therapeutic range established for humans for approximately 12 hr.

Diversity and Abundance of Nonculicid Biting Flies (Diptera) In A Zoo Environment.

The diversity of nonculicid biting flies was surveyed in Sunset Zoo, Manhattan, KS, by carbon dioxide-baited traps. A total of 8,399 nonculicid biting-fly females representing 32 species and 5 families were collected. Twenty-one biting midge (Ceratopogonidae: Culicoides) and 7 black fly (Simuliidae) species were collected, including new state records of 3 Culicoides and 1 simuliid. The species richness of Culicoides and Simuliidae within the zoo represents 72.4% and 41.2%, respectively, of the fauna known to occur in Kansas. Trap type significantly influenced (P < 0.05) collections of the 5 species analyzed, and trapping period affected 3 species. The diversity and abundance of nonculicid biting flies in the zoo as related to animal health and wellness is discussed.

Mucoepidermoid Carcinoma in the Skull of an Orange-winged Amazon Parrot (Amazona amazonica).

A 33-year-old female intact orange-winged Amazon parrot (Amazona amazonica) presented for a slowly growing mass over the right eye. A computed tomography scan performed with and without intravenous contrast revealed a heterogeneous mixed soft tissue and mineral-dense mass with a small area of non-contrast-enhancing fluid density located between the orbits at the caudal aspect of the nasal passages, with associated lysis of the right caudal nasal passage and the right frontal bone. Following euthanasia, the mass was found to consist of soft tissue between the right eye and nostril over the right frontal bone. Lysis of the underlying bone resulted in a bony defect leading into the infraorbital sinus along the dorsorostral aspect of the right eye. Histopathology revealed an unencapsulated, poorly demarcated, highly cellular neoplasm composed of islands and trabeculae of neoplastic cells embedded in abundant loose fibrovascular stroma which completely obliterated the cortical bone and sinuses of the rostral skull and infiltrated the surrounding muscle and soft tissue. Histologically, the tumor was consistent with a high-grade mucoepidermoid carcinoma, characterized by the presence of epidermoid, intermediate, and mucous-producing cell types. No evidence of metastasis was identified. The tissue of origin was suspected to be salivary or nasal mucous glands, but was difficult to confirm due to distortion of normal tissue architecture as a result of the tumor. Although mucoepidermoid carcinomas are a common salivary gland tumor in human medicine, they are not well recognized in avian species, and no specific case reports exist describing this pathology in an Amazon parrot. Despite the lack of distinct salivary glands in most avian species, mucoepidermoid carcinomas can occur, can cause significant clinical disease, and should be included as a differential diagnosis for avian patients presenting with similar lesions.

DIAGNOSIS AND SUCCESSFUL TREATMENT OF A POTENTIALLY ZOONOTIC DERMATOPHYTOSIS CAUSED BY MICROSPORUM GYPSEUM IN A ZOO-HOUSED NORTH AMERICAN PORCUPINE (ERETHIZON DORSATUM).

A female North American porcupine ( Erethizon dorsatum ) was evaluated for a unilateral pedal crusting and alopecic dermatopathy. Fungal culture and histopathology testing revealed Microsporum gypseum dermatophytosis. Treatment with topical miconazole was initiated and then discontinued after 9 days and changed to oral terbinafine. Twenty-eight days after initial examination, clinical signs were improving, and fungal cultures of the front foot, muzzle, and noninfected area along the dorsum were negative for M. gypseum. Visual exams were conducted on a regular basis. Eighty-three days after initial evaluation, clinical signs had completely resolved and repeat fungal cultures were negative. One of the animal's keepers was suspected to have acquired a dermal fungal infection 3 days after contact with this porcupine, and lesions had resolved after treatment with topical ketoconazole. To the authors' knowledge, this is the first report of M. gypseum diagnosed and treated in a captive North American porcupine. Veterinary staff and zookeepers should be aware of this potentially zoonotic infection.

Single-Dose Pharmacokinetics of Piperacillin/Tazobactam in Hispaniolan Amazon Parrots ( Amazona ventralis ).

To determine the pharmacokinetics of piperacillin/tazobactam in Hispaniolan Amazon parrots ( Amazona ventralis ), 8 healthy adult parrots of both sexes were used in a 2-part study. In a pilot study, piperacillin (87 mg/kg) in combination with tazobactam (11 mg/kg) was administered intramuscularly (IM) to 2 birds, and blood samples were obtained at 0, 0.5, 1, 1.5, 2, 3, 4, 6, 8, and 10 hours after administration. Based on the results obtained, a main study was done in which piperacillin/tazobactam was administered at 2 different doses. In 3 birds, the initial dose of piperacillin (87 mg/kg)/tazobactam (11 mg/kg) IM was administered, and in 3 birds, the dose was doubled to piperacillin (174 mg/kg)/tazobactam (22 mg/kg) IM. In all 6 birds, blood samples were obtained at 0, 5, 15, and 30 minutes and at 1, 1.5, 2, 2.5, 3, and 4 hours after administration. Quantification of plasma piperacillin and tazobactam concentrations was determined by validated liquid chromatography-mass spectrometry assay. Pharmacokinetic parameters were determined by noncompartmental analysis. After intramuscular administration, the mean ± standard error values of T1/2 (h) was 0.52 ± 0.05 and 0.32 ± 0.07, Tmax (h) was 0.28 ± 0.09 and 0.25 ± 0.10, Cmax (µg/mL) was 86.34 ± 20.62 and 9.03 ± 2.88, and Cmax/dose was 0.99 ± 0.24 and 0.83 ± 0.26 for piperacillin (87 mg/kg) and tazobactam (11 mg/kg), respectively. When the doses were doubled, the T1/2 (h) was 0.65 ± 0.08 and 0.34 ± 0.02, Tmax (h) was 0.28 ± 0.12 and 0.14 ± 0.06, Cmax (µg/mL) was 233.0 ± 6.08 and 22.13 ± 2.35, and Cmax/dose was 1.34 ± 0.03 and 1.02 ± 0.11 for piperacillin and tazobactam, respectively. Results indicate that piperacillin is rapidly absorbed and reaches high initial concentrations; however, it is also rapidly eliminated in the Hispaniolan Amazon parrot, and tazobactam has similar pharmacokinetics as piperacillin. Administration of piperacillin at 87 mg/kg IM q3-4h is recommended for this species to control infections attributed to susceptible bacteria with a minimum inhibitory concentration of ≤4 µg/mL.