CLINICAL AND PATHOLOGIC FINDINGS IN IGUANIDS WITH SODIUM URATE CHOLELITHIASIS.

Four green iguanas (Iguana iguana) and one blue iguana (Cyclura lewisi) from five facilities were diagnosed with sodium urate cholelithiasis. One case was diagnosed antemortem via ultrasonography, and the iguana underwent a choledochotomy for treatment. The other four cases were identified at necropsy. Pathologic hepatic and biliary changes were present in four of the five cases at necropsy. Histologically, four iguanas had hepatic fibrosis, three had bile duct hyperplasia, and one had cholangiohepatitis and pancreaticocholedochitis. Two iguanas had pathologic renal changes. This is the first report of sodium urate cholelithiasis in reptiles. This case series highlights the potential significant clinical disease caused by sodium urate cholelithiasis and the importance of biliary system evaluation. Further investigation is recommended to explore the pathogenesis of reptilian sodium urate cholelith formation.

A novel surgical technique for enucleation in rabbits to reduce the risk of intra- and post-operative orbital hemorrhage.

A 10-year-old male castrated Holland Lop rabbit (Oryctolagus cuniculus) was presented for severe ulcerative stromal keratitis of the right eye and a luxated hypermature cataract and glaucoma of the left eye. Staged bilateral enucleation was elected. A LigaSure™ electrosurgical bipolar vessel-sealing device was used as a means to minimize intraoperative and post-operative hemorrhage, especially that associated with the orbital venous plexus. The LigaSure™ was used to ligate and transect all extraocular muscles, the optic nerve bundle, and the base of the third eyelid with no complications encountered. Overall, the LigaSure™ was easy to use, resulted in minimal hemorrhage, and reduced surgery time. This is the first report of the use of a LigaSure™ to aid in the enucleation of a rabbit. Although only positive results were achieved as an alternative to conventional methodologies, its use in clinical practice should be that of caution until a larger study evaluating the long-term results is performed.

Modified Tail Amputation Technique in a Blue and Gold Macaw (Ara ararauna) With Uropygial Gland Adenocarcinoma.

A 33-year-old male blue and gold macaw (Ara ararauna) presented with a 5-month history of an ulcerated lesion and feather loss at the tail base. Two 4-mm biopsies obtained by the primary care veterinarian were consistent with uropygial gland adenocarcinoma. The bird was examined at the Veterinary Medical Teaching Hospital, University of California, and on physical evaluation, the dorsal and ventral surface of the tail base were devoid of feathers, ulcerated and crusted without an identifiable uropygial gland. Complete blood count, plasma biochemistry panel, whole-body radiographs, and an echocardiogram were performed before surgery. The bird was anesthetized, and a complete amputation of the tail was performed. The skin was incised with a radiofrequency electrosurgical system approximately 2 mm circumferentially cranial to the diseased tissue. The musculature was transected to the level of the vertebral column, disarticulating between the second and third caudal vertebrae and transecting the spinal cord with a no. 15 blade. Lateral vertebral processes of the second vertebra were removed with a rongeur. Coccygeus lateralis muscles and tensor fasciae latae muscles and skin were closed laterolaterally with 2 layers and 3-0 polydioxanone suture. The bird recovered uneventfully and was discharged after 6 days of hospitalization. The histopathological diagnosis was adenocarcinoma with squamous differentiation, marked scirrhous response, and superficial epithelial ulceration. It was determined that narrow margins of unaffected tissue were achieved from the pathological examination of submitted material. The bird was evaluated 24 days after surgery and again 3.5 months after surgery, without evidence of complications or recurrence. Approximately 10 days after the last reexamination, the bird was euthanatized after being found minimally responsive at home. A postmortem examination was not performed.

Pilot Study: Correlation of the Surface Skin Temperature Between the Leg and Foot Using Thermographic Imaging in Captive Hawks.

The purpose of this study was to determine whether the thermal image temperatures of the tibiotarsal scaled region of the raptor leg and the plantar surface of ipsilateral foot while perching were correlated. The correlation between leg and foot temperature was sought to determine whether remote imaging of the legs can be used as a reliable predictor of foot temperature. The right and left tarsometatarsal region (Leg) and metatarsal pad (Foot) of 10 captive hawks, including 8 red-tailed hawks (Buteo jamaicensis), 1 Harris's hawk (Parabuteo unicinctus), and 1 Swainson's hawk (Buteo swainsoni) were imaged once daily over 3 consecutive days. To account for conditions of the metatarsal pad that might affect the thermal image, 3 groups were identified: Normal, Active when mild hyperemia was present, and Suspect when abrasions were noted. A significant correlation was evident when thermography readings of the tarsometatarsal region (R.Leg and L.Leg) of the unrestrained bird were compared with readings from the plantar surface of the ipsilateral metatarsal pad when restrained (R.Foot and L.Foot). The correlations for R.Leg versus R.Foot (r = 0.81) and L.Leg versus L.Foot (r = 0.74) suggest that temperatures of the tarsometatarsal region of perching hawks measured by infrared thermography may be useful to screen and monitor for the presence of thermal changes associated with inflammation of the metatarsal pad in captive hawk species.

Evaluation of Orally Administered Atorvastatin on Plasma Lipid and Biochemistry Profiles in Hypercholesterolemic Hispaniolan Amazon Parrots (Amazona ventralis).

Atorvastatin is a synthetic statin administered in its active form and used for the treatment of dyslipidemias. In the current study, the effects of atorvastatin were evaluated on plasma lipid profiles and the potential for adverse effects after once daily PO dosing of atorvastatin for 30 days in Hispaniolan Amazon parrots (Amazona ventralis). Sixteen adult parrots (10 female, 6 male) with hypercholesterolemia were used for this study. Birds were assigned to 2 groups (treatment and control) of 8 parrots each (3 male, 5 female) after balancing for age, sex, originating institution, and baseline plasma cholesterol values. Compounded atorvastatin oral suspension (10 mg/kg) was administered PO once daily via gavage into the crop. Equivalent volumes of placebo suspension were administered to the control group. Plasma biochemistry and plasma lipid profile analysis (total cholesterol, high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TGs]) were analyzed on days 0, 14, and 30. Plasma samples and HDL-C fractions were evaluated for cholesterol and TG concentrations via enzymatic assays. Subtraction of HDL-C values from total cholesterol yielded the non-HDL-C concentration for each bird. Birds were routinely assessed for appetite, activity, and urofeces. Plasma atorvastatin concentrations were obtained from 7 of 8 birds in the treatment group from banked samples. Those samples were obtained on days 14 and 30, with drug administration 6 to 8 hours before collection. No significant differences were observed in total cholesterol, HDL-C, non-HDL-C, or TG between treatment and control groups at days 0, 14, and 30. Plasma atorvastatin concentrations were variable on day 14 (0.54-5.41 ng/ mL for 6 of 7 samples, with 1 outlier of 307 ng/mL) and on day 30 (0.79-6.74 ng/mL). No adverse effects were noted in any of the birds during the study period. When dosed PO at 10 mg/kg once daily, atorvastatin did not result in significant changes to plasma lipid profiles (eg, lowering of plasma total or non-HDL-C concentrations) at any time point during this study. Future studies to investigate pharmacokinetic and pharmacodynamic properties of atorvastatin in parrots may require increased doses and/or frequency of administration.

Acremonium and trichosporon fungal keratoconjunctivitis in a Leopard Gecko (Eublepharis macularius).

A 6-year-old male leopard gecko (Eublepharis macularius) was presented with a 2-year history of recurrent dysecdysis involving the ocular surface of both eyes. Ophthalmic examination revealed ocular surface desiccation and multifocal superficial ulcerative keratitis with patchy remnants of retained shed. Other abnormalities included stomatitis and mandibular and maxillary osteomyelitis. Topical and systemic antibiotic therapy, oral vitamin A, and improved husbandry conditions resolved the stomatitis and osteomyelitis but did not improve the ocular surface. Corneal cytology collected with a cytobrush revealed branching hyphae and budding yeast consistent with fungal keratitis. Fungal culture grew Acremonium sp. and Trichosporon sp. The addition of topical antifungal therapy improved the ocular surface health, but the patient was euthanized 7 weeks after initial presentation for persistent vomiting and dyspnea. Necropsy was declined. This case describes the first case of fungal keratitis caused by Acremonium sp. and Trichosporon sp. in a reptile.

Blind free-living kiwi offer a unique window into the ecology and evolution of vertebrate vision.

The first report of multiple, blind, wild birds in good health suggests vision is not necessary for the survival of kiwi.

Ocular anatomy of the black pacu (Colossoma macropomum): gross, histologic, and diagnostic imaging.

OBJECTIVE: To describe the ocular anatomy of the black pacu (Colossoma macropomum), a freshwater teleost fish of the Amazon River basin, including an unusual choroid laden with adipose tissue. PROCEDURES: Three adult black pacu were anesthetized and examined clinically and with ocular ultrasonography, then euthanized. Three fish were euthanized and their heads imaged immediately postmortem using computed tomography. One fish was euthanized and its exenterated eyes imaged by high-resolution magnetic resonance imaging. The exenterated eyes of all seven fish were fixed in formalin; eyes from three fish were examined grossly and histologically. Additionally, archived histologic sections from two smaller black pacu specimens were examined. RESULTS: Findings were consistent among the ocular imaging modalities used. Intrinsic to the sclera were circumferential ossicles and scleral cartilage. The lens was spherical and protruded through the ovoid pupil with an aphakic space inferiorly when the accommodative mechanism was relaxed under anesthesia. Both a small falciform process and epiretinal vasculature were present in the posterior segment. The retina was cone-rich, and processes of the retinal pigment epithelium enveloped the photoreceptor outer segments. Remarkably, the choroid occupied one-third of the anteroposterior length of the globe; histology confirmed that the bulk of the choroid was composed of adipose tissue. CONCLUSIONS: The eye of the pacu overall is typical of teleosts but has the notable and consistent finding of a substantive store of choroidal fat of unknown function.

Lipoidal corneal degeneration in aged falcons.

OBJECTIVE: To present a case series of idiopathic lipoidal corneal degeneration in falcons. ANIMALS STUDIED: Five falcons including three peregrine falcons (Falco peregrinus), one prairie falcon (Falco mexicanus), and one red-naped shaheen (Falco peregrinus babylonicus) were observed to develop slowly progressive corneal opacification that began at the temporal limbus and extended centripetally across the cornea over a period of years. Four of the birds were over 20 years old. PROCEDURES: All animals underwent complete ophthalmic examinations. A red-naped shaheen underwent ocular imaging via spectral-domain optical coherence tomography. Two peregrine falcons were euthanized due to declining health, and their eyes were examined histologically. RESULTS: The opacities were pale and granular, with frequent vascularization associated perilimbally. Diffuse neutral lipid was observed in stromal cells throughout the corneal stroma of both clear and opaque areas of the cornea, sparing only the acellular anterior limiting lamina. Clusters of cholesterol crystals surrounded by macrophages were present in the mid-stroma. Fibrosis was evident in a subepithelial location, which separated the epithelium from the anterior limiting lamina. Ultrastructurally, diffuse vacuolization of the keratocytes was observed. No other ophthalmic or systemic abnormalities were noted. CONCLUSIONS: Results suggest that lipid degeneration occurs rarely in captive falcons of advanced age. The underlying cause is unclear. Though unsubstantiated, possible contributing factors include dyslipoproteinemia, corneal trauma, diet, and age-related alterations in corneal metabolism. The initiation of pathology at the temporal limbus, as well as slow progression, suggests that exposure contributes to the onset and progression of this unique keratopathy.

Evaluation of the Thermal Antinociceptive Effects of a Sustained-Release Buprenorphine Formulation After Intramuscular Administration to American kestrels ( Falco sparverius).

Previous studies have validated the clinical use of opioids with µ-receptor affinities for pain management in raptors. Buprenorphine has a longer duration of action and minimal adverse effects when compared with other opioids in American kestrels ( Falco sparverius). To evaluate the thermal antinociceptive effects, sedative effects, and duration of action of sustained-release buprenorphine given intramusculary in American kestrels, 12 adult kestrels (8 females and 4 males) were used in a randomized masked complete-crossover experimental design. Buprenorphine SR LAB (1.8 mg/kg) or a control solution were administered intramuscularly. Foot withdrawal response to a thermal stimulus was determined 1 hour before (baseline) and at 1.5, 6, 12, 24, 48, and 72 hours after treatment administration. Agitation-sedation scores were determined 3-5 minutes before each time point, and adverse effects were monitored at these times. Buprenorphine SR LAB significantly increased thermal thresholds at 6, 12, and 24 hours and resulted in mild sedation according to the mean sedation-agitation scores comparing the treatment and control groups. Depending on the severity and type of pain, adjunctive therapy, and individual response, Buprenorphine SR LAB administered at 1.8 mg/kg IM to American kestrels would require administration every 24 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and other Falconiformes, Accipitriformes, and Strigiformes to establish accurate dosing recommendations.

Pharmacokinetics of a Sustained Release Formulation of Buprenorphine After Intramuscular and Subcutaneous Administration to American Kestrels ( Falco sparverius ).

Previous studies have validated the clinical use of opioids with µ-receptor affinities for pain management in raptors. Buprenorphine appears to have a longer duration of action and minimal adverse effects when compared to other opioids in American kestrels ( Falco sparverius ). To determine the pharmacokinetics of a sustained release formulation of buprenorphine in kestrels, we administered a commercially available product (Buprenorphine SR-LAB; Wildlife Pharmaceuticals, Windsor, CO, USA) intramuscularly and subcutaneously to adult kestrels in a partial-crossover experimental design study. A total of 12 birds (6 males and 6 females) were assigned randomly to 3 groups of 4 birds each. A single dose of Buprenorphine SR-LAB (1.8 mg/kg) was administered intramuscularly (IM), and blood samples were collected at 0.25, 3, and 24 hours (n = 4); 1, 6, and 48 hours (n = 4); and 2, 12, and 72 hours (n = 4) after drug administration. Plasma buprenorphine concentrations were measured by tandem liquid chromatography-mass spectrometry. Pharmacokinetic parameters were determined by use of least squares linear regression and noncompartmental analysis of naïve pooled data. After 1 year, the same dose of buprenorphine was administered subcutaneously (SC) to 12 birds divided into 3 groups as previously, and blood samples were collected at the same times after drug administration. Maximum plasma buprenorphine concentration was measured at 15 minutes after IM and SC administration. Mean plasma buprenorphine concentrations were >1 ng/mL for 48 hours after IM and SC administration. The elimination half-life was 13.5 and 11.1 hours for IM and SC administration, respectively. Depending on the severity and type of pain, adjunctive therapy, and the individual response, Buprenorphine SR-LAB administered at 1.8 mg/kg IM or SC to American kestrels would require administration every 12 to 72 hours to manage pain. Further pharmacodynamic and clinical evaluations are warranted in kestrels and other raptors to establish accurate dosing recommendations.

Pharmacokinetics of a Sustained-release Formulation of Meloxicam After Subcutaneous Administration to Hispaniolan Amazon Parrots (Amazona ventralis).

Meloxicam has been shown to have a safe and favorable pharmacodynamic profile with individual variability in Hispaniolan Amazon parrots (Amazona ventralis). In the current study, we determined the pharmacokinetics of a sustained-release formulation of meloxicam after subcutaneous administration to Hispaniolan Amazon parrots. Twelve healthy adult parrots, 6 males and 6 females, were used in the study. Blood samples were collected before (time 0) and at 0.5, 1, 2, 6, 12, 24, 48, 72, 96, and 120 hours after a single dose of the sustained-release meloxicam formulation (3 mg/kg SC). Plasma meloxicam concentrations were measured by high-pressure liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis. Plasma concentrations reached a mean Cmax of 23.4 µg/mL (range, 14.7-46.0 µg/mL) at 1.8 hours (range, 0.5-6 hours), with a terminal half-life of 7.4 hours (range, 1.4-40.9 hours). Individual variation was noticeable, such that some parrots (4 of 12 birds) had very low plasma meloxicam concentrations, similar to the high variability reported in a previous pharmacokinetic study of the standard meloxicam formulation in the same group of birds. Two birds developed small self-resolving scabs at the injection site. On the basis of these results, the sustained-release meloxicam formulation could be administered every 12 to 96 hours in Hispaniolan Amazon parrots to manage pain. Because of these highly variable results, the use of this formulation in this species cannot be recommended until further pharmacokinetic, safety, and pharmacogenomic evaluations are performed to establish accurate dosing recommendations and to understand the high pharmacokinetic variability.

EFFECTS OF EXERCISE ON THE PLASMA LIPID PROFILE IN HISPANIOLAN AMAZON PARROTS (AMAZONA VENTRALIS) WITH NATURALLY OCCURRING HYPERCHOLESTEROLEMIA.

Hypercholesterolemia is common in psittacines, and Amazon parrots ( Amazona spp.) are particularly susceptible. Associations have been demonstrated between naturally occurring and experimentally induced hypercholesterolemia and atherosclerosis in psittacines. Daily exercise improves lipid metabolism in humans and other mammals, as well as pigeons and chickens, under varying experimental conditions. Hispaniolan Amazon parrots ( Amazona ventralis ) with naturally occurring hypercholesterolemia (343-576 mg/dl) were divided into two groups. An exercised group (n = 8) was housed as a flock and exercised daily with 30 min of aviary flight and 30 min walking on a rotating perch. A sedentary control group (n = 4) was housed in individual cages with no exercise regime. A plasma lipid panel, including total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, and triglycerides, was validated for this species. Body weight, chest girth, and the lipid panel were measured at 0, 61, and 105 days. Hematology and plasma biochemistry were measured at 0 and 105 days. Weight and girth were significantly lower in exercised than sedentary parrots at 61 and 105 days. HDL-C concentrations were significantly higher in exercised parrots at 61 days but returned to near baseline by 105 days. There were no significant changes in hematology, biochemistry, or other lipid panel parameters. Results were similar to studies in humans and animal models, in which increased HDL-C was the most consistent effect of exercise on circulating lipid and lipoprotein parameters. The return toward baseline HDL-C may have resulted from decreased participation in aviary flight. Additional investigation will be required to determine the amount of exercise and change in circulating lipid-related parameters necessary to improve long-term wellness in psittacine species predisposed to hypercholesterolemia.

Spectral domain optical coherence tomography imaging of spectacular ecdysis in the royal python (Python regius).

OBJECTIVE: To describe using spectral domain optical coherence tomography (SD-OCT), digital slit-lamp biomicroscopy, and external photography, changes in the ophidian cuticle, spectacle, and cornea during ecdysis. ANIMALS STUDIED: Four normal royal pythons (Python regius). PROCEDURES: Snakes were assessed once daily throughout a complete shed cycle using nasal, axial, and temporal SD-OCT images, digital slit-lamp biomicroscopy, and external photography. RESULTS: Spectral domain optical coherence tomography (SD-OCT) images reliably showed the spectacular cuticle and stroma, subcuticular space (SCS), cornea, anterior chamber, iris, and Schlemm's canal. When visible, the subspectacular space (SSS) was more distended peripherally than axially. Ocular surface changes throughout ecdysis were relatively conserved among snakes at all three regions imaged. From baseline (7 days following completion of a full cycle), the spectacle gradually thickened before separating into superficial cuticular and deep, hyper-reflective stromal components, thereby creating the SCS. During spectacular separation, the stroma regained original reflectivity, and multiple hyper-reflective foci (likely fragments from the cuticular-stromal interface) were noted within the SCS. The cornea was relatively unchanged in character or thickness throughout all stages of ecdysis. Slit-lamp images did not permit observation of these changes. CONCLUSIONS: Spectral domain optical coherence tomography (SD-OCT) provided excellent high-resolution images of the snake anterior segment, and especially the cuticle, spectacle, and cornea of manually restrained normal snakes at all stages of ecdysis and warrants investigation in snakes with anterior segment disease. The peripheral spectacle may be the preferred entry point for diagnostic or therapeutic injections into the SSS and for initiating spectacular surgery.

Carrageenan-induced inflammation elicits behavioral changes in cockatiels (Nymphicus hollandicus) for potential pain scale development.

OBJECTIVE: To evaluate behaviors associated with inflammatory pain induced by carrageenan injection in the cockatiel and determine interobserver agreement. ANIMALS: 16 adult cockatiels. METHODS: Cockatiels were randomly assigned as either treatment (carrageenan injection) or control (sham injection) group. The treatment group received a subcutaneous injection of 0.05 mL of a 1% lambda carrageenan solution into the left footpad. Following treatment or control procedures, all cockatiels were video recorded individually for 9.5 hours. Ten minutes of video at each of 11 time points postinjection and/or handling were evaluated by 3 different observers. Twenty-five behaviors within 6 categories (resting, locomotion, maintenance, intake, interaction with environment, and limb and body posture) were assessed, in addition to crest position and mentation. Differences in individual behaviors tallies were assessed using serial Wilcoxon sum rank tests. Interobserver agreement was assessed using an intraclass correlation coefficient for a 2-way design for consistency among multiple observers. RESULTS: Treatment cockatiels exhibited significantly increased focal preening (q = .023) and increased burst preening (q = .036), while control cockatiels spent significantly more time in an upright stance (q = .036). Although the remainder of behaviors observed were not statistically significant between groups, additional variables of interest seen more frequently in treatment cockatiels included non-weight-bearing stance, holding of the body low, and being nonvigilant. The level of agreement between observers was variable based on the specific behaviors; nevertheless, the dynamic behaviors were substantial to strong. CLINICAL RELEVANCE: Carrageenan-induced inflammation-associated behaviors may be valuable in developing a pain scale and evaluating mild inflammatory pain in small psittacine species.

Grey parrot (Psittacus erithacus) beak papillae and nerves identified using novel 2-D and 3-D imaging modalities.

OBJECTIVE: The avian beak is a complex organ containing bone, neurovascular tissue, and keratinized covering (rhamphotheca). Nerve-rich papillae extend through bone into rhamphotheca providing sensory input from the beak tip. Beak trimming is a common procedure in avian species and is used for corrective, cosmetic, and behavioral modification purposes. Yet, practitioners are not well versed in complete beak anatomy, and therefore, beak trimming often disregards neurovasculature, injuring the patient and hampering recovery. Here, using comprehensive anatomical description, we aim to provide recommendations on how to safely perform beak trimming without damaging underlying sensory papillae. ANIMALS: Here, we evaluated beaks of 2 deceased grey parrots (Psittacus erithacus). PROCEDURES: In one, we used a novel stain and microcomputed tomography to visualize papillae in the upper and lower beaks. In a second, we hand isolated the upper and lower beak dermal papillae and used high-resolution photography plus traditional paraffin histology. RESULTS: Papillae and their nerves were easily identified in these 2- and 3-dimensional approaches. This allowed us to determine the approximate lengths of papillae within the upper and lower beak. CLINICAL RELEVANCE: Based on these findings, the authors recommend lateral radiographs of the bird's head and beak to identify the location of the underlying bone relative to the overlying rhamphotheca before performing beak trims. Specifically in grey parrots, the authors recommend the upper and lower beak should not be trimmed closer than 8 to 10 mm from the underlying bone. Further work is needed to support these recommendations and provide guidelines for other species.

Absorption of grapiprant in red-tailed hawks (Buteo jamaicensis) is decreased when administered with food.

OBJECTIVE: Describe the pharmacokinetics of grapiprant administered orally with food to red-tailed hawks (RTHAs; Buteo jamaicensis) and compare the results with previously described grapiprant pharmacokinetics administered without food in this species. ANIMALS: 6 healthy adult RTHA (3 males, 3 females) under human care. PROCEDURES: A single dose of grapiprant (30 mg/kg) was given orally to RTHAs, followed by force-feeding. Blood samples were obtained at 14 time points for 120 hours postgrapiprant administration. Plasma concentrations of grapiprant were measured via tandem liquid chromatography-mass spectrometry. Nonparametric superimposition using pharmacokinetic modeling software used plasma concentrations to calculate simulations of grapiprant plasma concentrations for 30 mg/kg administered orally with food every 12 hours. RESULTS: The arithmetic mean maximum plasma concentration was 405.8 ng/mL, time to maximum plasma concentration was 16 hours, and harmonic mean terminal half-life was 15.6 hours. Simulations determined 30 mg/kg every 12 hours could attain minimum effective concentrations (> 164 ng/mL) reported in dogs for a sustained period of approximately 20 hours. CLINICAL RELEVANCE: Grapiprant plasma concentrations were achieved above the canine therapeutic concentrations within 16 hours postmedication. Mean concentrations were maintained for approximately 20 hours. Simulations support a dosing frequency of 12-hour intervals with food reaching minimum effective concentrations established for canines, although it is unknown whether these plasma concentrations are therapeutic for birds. Bioaccumulation was not noted on simulations secondary to increased grapiprant administration. Further research including multidose assessments at this current dose with food, in vitro pharmacological characterization, and pharmacodynamic studies in this species are warranted.

Pharmacokinetics of butorphanol tartrate in a poloxamer P407 gel formulation administered to orange-winged Amazon parrots (Amazona amazonica).

OBJECTIVES: To determine the pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after subcutaneous administration to orange-winged Amazon parrots (Amazona amazonica). ANIMALS: Six orange-winged Amazon parrots, ages 28 to 45 years. PROCEDURES: A sterile formulation of butorphanol in P407 (But-P407) as a 25% gel was created to produce a concentration of 8.3 mg/mL. The formulation was administered SC at a dose of 12.5 mg/kg to all birds. Blood samples were collected at baseline prior to injection (time 0) and then at 0.08, 0.5, 1, 1.5, 4, 8, and 12 hours after drug administration. Butorphanol concentrations were quantitated via liquid chromatography-tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis and a commercially available software program. RESULTS: Plasma concentrations of butorphanol remained > 100 ng/mL for > 4 hours for some birds (3/5) but were < 100 ng/mL for all birds by the 8-hour mark. Cmax and tmax were 346.9 ± 233.7 ng/mL and 1.3 ± 0.274 hours, respectively. Half-life was 1.56 ± 0.445 hours. No adverse effects were detected. CLINICAL RELEVANCE: Butorphanol was absorbed from the But-P407 25% by the majority of the orange-winged Amazon parrots in this study (3/5), although to a lesser extent compared to Hispaniolan Amazon parrots. Absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would be expected to provide antinociception for 4 to 8 hours, although pharmacodynamic studies in this species using this formulation have not demonstrated this.

Pharmacokinetics of butorphanol after intravenous, intramuscular, and oral administration in Hispaniolan Amazon parrots (Amazona ventralis).

Previous studies have validated the clinical use of opioids with kaap-receptor affinities for pain management in birds. Butorphanol, a kappa opioid receptor agonist and a mu opioid receptor antagonist, is currently considered by many clinicians to be the opioid of choice for this use. However, despite studies reporting the analgesic properties of butorphanol in psittacine birds, dosing intervals have not been established for any psittacine species. The goals of this study in the Hispaniolan Amazon parrot (Amazona ventralis) were to evaluate the pharmacokinetics of butorphanol tartrate after intravenous (IV), intramuscular (IM), and oral (PO) administration and to determine the bioavailability of butorphanol tartrate after oral administration. Twelve Hispaniolan Amazon parrots were used in the study, with a complete-crossover experimental design and a 3-month period separating each part of the study. The birds were randomly assigned to 3 groups (n = 4) for each stage. Butorphanol tartrate was administered once at a dose of 5 mg/kg in the basilic vein or pectoral muscles or as an oral solution delivered via feeding tube into the crop for the IV, IM, and PO studies, respectively. After butorphanol administration, blood samples were collected at 1, 5, 15, 30, 60, 90, 120, 180, and 240 minutes for the IV and IM studies and at 5, 15, 30, 60, 90, 120, 180, 240, and 300 minutes for the PO study. Because of the size limitation of the birds, naive pooling of datum points was used to generate a mean plasma butorphanol concentration at each time point. For each study, birds in each group (n = 4) were bled 3 times after dosing. Plasma butorphanol concentrations were determined by high-performance liquid chromatography/tandem mass spectrometry, and pharmacokinetic parameters were calculated. Butorphanol tartrate was found to have high bioavailability and rapid elimination following IM administration. In contrast, oral administration resulted in low bioavailability (< 10%), thus precluding the use of this route of administration for clinical purposes. Based on these results, in Hispaniolan Amazon parrots, butorphanol tartrate dosed at 5 mg/kg IV or IM would have to be administered every 2 and 3 hours, respectively, to maintain plasma concentrations consistent with published therapeutic levels. To our knowledge, this is the first published study presenting the pharmacokinetic analysis of butorphanol tartrate in a psittacine species as well as the first study presenting pharmacokinetic analysis of butorphanol after oral administration in any avian species.

Pharmacokinetics of grapiprant administered to red-tailed hawks (Buteo jamaicensis) after food was withheld for 24 hours.

OBJECTIVE: To identify an oral dose of grapiprant for red-tailed hawks (RTHAs; Buteo jamaicensis) that would achieve a plasma concentration > 164 ng/mL, which is considered therapeutic for dogs with osteoarthritis. ANIMALS: 6 healthy adult RTHAs. PROCEDURES: A preliminary study, in which grapiprant (4 mg/kg [n = 2], 11 mg/kg [2], or 45 mg/kg [2]) was delivered into the crop of RTHAs from which food had been withheld for 24 hours, was performed to obtained pharmacokinetic data for use with modeling software to simulate results for grapiprant doses of 20, 25, 30, 35, and 40 mg/kg. Simulation results directed our selection of the grapiprant dose administered to the RTHAs in a single-dose study. Plasma grapiprant concentration, body weight, and gastrointestinal signs of RTHAs were monitored. RESULTS: On the basis of results from the preliminary study and simulations, a grapiprant dose of 30 mg/kg was used in the single-dose study. The geometric mean maximum observed plasma concentration of grapiprant was 3,184 ng/mL, time to maximum plasma grapiprant concentration was 2.0 hours, and the harmonic mean terminal half-life was 17.1 hours. No substantial adverse effects were observed. CONCLUSIONS AND CLINICAL RELEVANCE: Although the single dose of grapiprant (30 mg/kg) delivered into the crop achieved plasma concentrations > 164 ng/mL in the RTHAs, it was unknown whether this concentration would be therapeutic for birds. Further research that incorporates multidose assessments, safety monitoring, and pharmacodynamic data collection is warranted on the use of grapiprant in RTHAs from which food was withheld versus not withheld.