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.
Six healthy, 4-month-old New Zealand White rabbits (3 male, 3 female).
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.
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.
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.
To evaluate the effects of a dexmedetomidine-midazolam-ketamine (DMK) combination administered IM to captive red-footed tortoises (Chelonoidis carbonaria).
12 healthy adult red-footed tortoises.
In a prospective experimental study, DMK (0.1, 1.0, and 10 mg/kg, respectively) was administered IM as separate injections into the right antebrachium. Atipamezole (0.5 mg/kg, IM) and flumazenil (0.05 mg/kg, SC) were administered into the left antebrachium 60 minutes later. Times to the first treatment response and maximal treatment effect after DMK administration and time to recovery after reversal agent administration were recorded. Vital signs and reflexes or responses to stimuli were assessed and recorded at predetermined intervals.
DMK treatment produced deep sedation or light anesthesia for ≥ 20 minutes in all tortoises. Induction and recovery were rapid, with no complications noted. Median times to first response, maximum effect, and recovery were 4.5, 35, and 14.5 minutes, respectively. Two tortoises required additional reversal agent administration but recovered < 20 minutes after the repeated injections. Mean heart and respiratory rates decreased significantly over time. All animals lost muscle tone in the neck and limbs from 35 to 55 minutes after DMK injection, but other variables including palpebral reflexes, responses to mild noxious stimuli (eg, toe pinching, tail pinching, and saline ([0.9 NaCl] solution injection), and ability to intubate were inconsistent.
CONCLUSIONS AND CLINICAL RELEVANCE
DMK administration produced deep sedation or light anesthesia with no adverse effects in healthy adult red-footed tortoises. At the doses administered, deep surgical anesthesia was not consistently achieved. Anesthetic depth must be carefully evaluated before performing painful procedures in red-footed tortoises with this DMK protocol.
Objective—To describe changes in venous blood gas analytes during isoflurane anesthesia in black-tailed prairie dogs (Cynomys ludovicianus).
Animals—16 black-tailed prairie dogs.
Procedures—Black-tailed prairie dogs were placed in an anesthesia chamber for induction of general anesthesia, which was maintained with isoflurane in oxygen delivered via mask. Immediately following anesthetic induction, a venous blood sample was obtained from the medial saphenous vein; a second venous blood sample was obtained just prior to anesthetic gas shutoff. An evaluation of venous blood gas analytes was performed on each sample. General linear mixed models with repeated measures were used for data analyses.
Results—Median anesthetic time was 90 minutes (range, 60 to 111 minutes). A significant increase from immediately after induction to completion of anesthesia was observed in Pco2 and mean blood chloride ion, BUN, and creatinine concentrations. A decrease in Po2, mean blood pH, and anion gap was observed from induction of anesthesia to completion. No significant differences during anesthesia were observed in mean base excess or blood bicarbonate, sodium, potassium, calcium, magnesium, blood glucose, lactate, and total CO2 concentrations. No complications occurred during or after anesthesia for any animal.
Conclusions and Clinical Relevance—Examination of prairie dogs often requires general anesthesia, with isoflurane currently the inhalation agent of choice. Results suggested respiratory acidosis and relative azotemia may occur during isoflurane anesthesia of prairie dogs. Given the increased risk associated with anesthesia in small mammals and the propensity for respiratory disease in prairie dogs, insight into physiologic changes associated with isoflurane anesthesia in healthy prairie dogs can aid in perioperative evaluation and anesthetic monitoring in this rodent species.
To identify potential risk factors for death following IV or intraosseous (IO) administration of contrast medium in birds undergoing CT scans.
120 birds that underwent 134 contrast-enhanced CT scans.
Medical records of birds of any species that underwent a CT scan which included administration of nonionic iodinated contrast medium from June 2013 to February 2020 were included. Information on birds and use of contrast medium was extracted from the medical records as well as information on deaths following IV or IO administration of contrast medium.
6 birds died shortly following administration of contrast medium. Necropsies were performed in 3 birds (2 cockatiels and 1 macaw), and all had lesions associated with the respiratory tract. When body weight was used as a binary variable to compare odds of death between small birds (≤ 150 g [0.33 lb]) and large birds (> 150 g), small birds had a 97-fold increased odds (OR, 97.5; 95% CI, 9.8 to 966.0) of dying following contrast medium administration. Following 131 CT scans with contrast medium administration (3 scans were excluded because of perivascular or subcutaneous leakage of contract medium), small birds had a mortality rate of 45.4% (5/11), compared with a mortality rate of 0.8% (1/120) for large (> 150 g) birds. Other variables (ie, sex, age, anesthesia or sedation, sedation protocol, and type of contrast medium) were not significantly associated with death after contrast medium administration.
CONCLUSIONS AND CLINICAL RELEVANCE
Although the administration of contrast medium cannot be conclusively confirmed as the cause of death in these birds, the high mortality rate for small birds coupled with the temporality of the event following contrast medium administration justifies the cautious use of contrast medium in small sick psittacine birds. (J Am Vet Med Assoc 2021;259:77–83)
To examine the pharmacokinetics and ex vivo pharmacodynamics of oral firocoxib administration in New Zealand White rabbits (Oryctolagus cuniculus).
6 healthy New Zealand White rabbits.
Pharmacokinetics were determined from plasma concentrations measured via ultra performance liquid chromatography-tandem mass spectrometry after oral administration of firocoxib at a dose of 3.74 to 4.20 mg/kg. Pharmacokinetic analysis was performed using non compartmental methods. Pharmacodynamics of firocoxib were evaluated by measuring plasma concentrations of thromboxane and prostaglandin via ELISAs as surrogate markers of cyclooxygenase enzyme isoform inhibition.
The terminal rate constant was 0.07 hours (range, 0.05 to 0.11 h). The mean maximum concentration (Cmax) and time to Cmax were 0.16 µg/mL and 3.81 hours (range, 2.0 to 8.0 h), respectively. Mean residence time was 15.02 hours. Mean elimination half-life was 9.12 hours. For the pharmacodynamic analysis, firocoxib administration did not demonstrate a significant difference between any time point for prostaglandin E2 and only a significant difference between 24 and 48 hours for thromboxane B2.
Although the pharmacokinetic research supports that plasma firocoxib concentrations that would be therapeutic in dogs are achieved in rabbits, the pharmacodynamic results do not demonstrate a significant difference in levels of cyclooxygenase-2 inhibition, which indirectly reflects the anti-inflammatory effects of the drug. Further pharmacodynamic studies and multidose studies are warranted to determine the efficacy and safety of this drug in rabbits.
To determine the pharmacokinetic parameters of a high-concentration buprenorphine formulation after a single SC dose in American flamingos (Phoenicopterus ruber).
6 healthy adult American flamingos (3 males and 3 females).
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.
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.
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.
To describe the clinical presentation, treatment, and treatment outcomes for companion rats (Rattus norvegicus) diagnosed with lymphoma.
All rats that presented to the exotics service and underwent postmortem examination during the time period of 2008 through 2020 were evaluated.
The medical records of 35 rats were evaluated for an ante- or postmortem diagnosis of lymphoma. Cases with a diagnosis of lymphoma were further reviewed for signalment, presenting complaint, clinical signs observed on physical exam, diagnostic testing performed, and treatments administered. Postmortem gross and histologic findings were reviewed.
7 out of 35 rats were diagnosed with lymphoma, either ante-mortem or postmortem. The most common presenting complaint that was present in all rats with lymphoma was respiratory abnormalities. Five out of 7 rats had radiographs performed, all of which had abnormalities noted in the thoracic cavity including pulmonary nodules, cranial mediastinal widening, or alteration to the cardiac silhouette. Diagnosis via cytologic aspirates was performed in 2 cases and each was diagnostic for lymphoma; however, even with treatment, survival time following initiation of chemotherapy was short (less than or equal to 24 days). The definitive diagnosis in the remainder of the cases was via necropsy.
Results suggest that lymphoma is a common neoplastic disease in rats and a thorough diagnostic work-up is indicated in any rat that presents for general malaise or respiratory signs.
To document the clinical signs, diagnosis, and treatment of urolithiasis in green iguanas (Iguana iguana) and to report on the composition of uroliths from green iguanas submitted to the Minnesota Urolith Center for analysis.
21 green iguanas with urolithiasis.
Medical record databases of multiple veterinary teaching hospitals were searched from 1996 through 2020. Emails were sent to all facilities that submitted a urolith from a green iguana to the Minnesota Urolith Center from 1996 through 2020. Signalment; presenting complaint; physical examination findings; hematologic, biochemical, and diagnostic imaging findings; treatment; necropsy results; and survival times were described for each patient.
Iguanas most commonly presented with nonspecific clinical signs, but 9 of the 21 iguanas had clinical signs associated with the urogenital tract. Twelve iguanas had a palpable mass in the caudal coelom. All uroliths were visible on radiographs. Surgery was performed on 15 iguanas; 3 died secondary to intra- or postoperative complications. Iguanas that underwent surgery had a median survival time of 39 months. Necropsy was performed on 5 iguanas, and urolithiasis contributed to the decision to euthanize or was the cause of death for 4. Uroliths from 132 iguanas were analyzed, and all were composed of 100% uric acid salts.
Green iguanas with urolithiasis may not have clinical signs or physical examination findings associated with the urinary system, and hematologic and biochemical abnormalities are nonspecific. Green iguanas should be routinely examined for uroliths, and surgical treatment should be pursued.
OBJECTIVE To determine the pharmacokinetics and adverse effects following SC administration of ceftiofur crystalline free acid (CCFA) in New Zealand White rabbits.
ANIMALS 6 adult sexually intact female New Zealand White rabbits.
PROCEDURES Each rabbit was administered 40 mg of CCFA/kg SC. A blood sample was obtained immediately before (0 minutes), at 5 and 30 minutes after, and at 1, 1.5, 2, 3, 4, 8, 12, 24, 48, 72, 95, 120, 144, and 168 hours after administration, and plasma concentrations of ceftiofur free acid equivalents (CFAE) were measured. Pharmacokinetic parameters were calculated. For each rabbit, body weight, food consumption, fecal output, and injection site were monitored. Minimum inhibitory concentrations of ceftiofur for 293 bacterial isolates from rabbit clinical samples were determined.
RESULTS Mean ± SD peak plasma concentration of CFAE and time to maximum plasma concentration were 33.13 ± 10.15 μg/mL and 1.75 ± 0.42 hours, respectively. The mean terminal half-life of CFAE was 42.6 ± 5.2 hours. Plasma CFAE concentration was > 4 μg/mL for approximately 24 hours and > 1 μg/mL for at least 72 hours after CCFA administration. An apparently nonpainful subcutaneous nodule developed at the injection site in 3 of 6 rabbits.
CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that CCFA (40 mg/kg) could be administered SC every 24 to 72 hours to New Zealand White rabbits to treat infections with ceftiofur-susceptible bacteria. Single-dose administration of CCFA resulted in minimal adverse effects. Additional studies are needed to evaluate the effects of repeated CCFA administration in New Zealand White rabbits.