Investigation of suspected gadolinium neurotoxicity in a dog.

Gadolinium-based contrast agents are used across species to better visualize abnormalities during MRI and are considered generally safe in clinical practice. The aim of this study was to investigate central nervous system (CNS) gadolinium deposition in 11 dogs that had an MRI performed, received 0.22 mL/kg (0.1 mmol/kg) of gadopentetate dimeglumine, and were necropsied on the same hospital admission. The index case was a 5-year-old castrated male Australian Shepherd that presented for ataxia and following MRI developed seizure-like activity that became refractory to anticonvulsant therapy. Gadolinium concentration was quantified in CNS tissues by inductively-coupled plasma mass spectrometry and was 43-fold higher in the index case. These findings suggest the possibility of gadolinium toxicity in select patients.

Pharmacokinetics and tissue concentrations of firocoxib in sows following oral administration.

The objectives of this study were to describe the pharmacokinetics of firocoxib following oral (PO) dosing and intravenous (IV) injection in sows. Seven healthy sows were administered 0.5 mg firocoxib/kg IV. Following a 23-d washout period, sows were administered firocoxib at 4.0 mg firocoxib/kg PO. Blood samples were collected at predetermined times for 72 hr after IV and 120 hr after PO administration. Plasma firocoxib concentration was measured using UPLC-MS/MS, and pharmacokinetic analysis was performed using noncompartmental procedures. Tissue firocoxib concentrations were determined at 5, 10 (n = 2/time point), and 21 d (n = 3) after PO administration. The geometric mean half-life following IV and PO administration was 16.6 and 22.5 hr, respectively. A mean peak plasma concentration (Cmax) of 0.06 µg/ml was recorded at 7.41 hr (Tmax ) after oral administration. Mean oral bioavailability was determined to be 70.3%. No signs of NSAID toxicity were observed on macroscopic and microscopic investigation. Firocoxib was detected in the skin with subcutaneous fat (0.02 µg/g) of one of three sows at 21 days postadministration. Additional work to establish appropriate meat withhold intervals in sows is required. Firocoxib was readily absorbed following PO administration. Further work is needed to better understand the analgesic effects for sows and piglets nursing sows administered firocoxib.

Successful treatment of bifenthrin toxicosis using therapeutic plasma exchange.

OBJECTIVE: To describe a case of bifenthrin toxicosis in a dog with a successful outcome following the use of therapeutic plasma exchange (TPE) and intralipid therapy. CASE SUMMARY: An 8-month-old female neutered poodle mix dog ingested an unknown amount of powered bifenthrin, which resulted in acutely altered mentation, cranial nerve deficits, and intractable tremors that persisted in severity despite aggressive medical management to include intravenous fluids, intravenous lipid emulsion, anticonvulsant medications, and methocarbamol. TPE was initiated after lack of significant clinical improvement 12 hours after initial presentation. The dog underwent cardiopulmonary arrest (CPA) following approximately 1 plasma volume equivalent exchange. The dog was successfully resuscitated and showed marked improvement 12 hours postarrest and post-TPE treatment. Serum bifenthrin concentrations were analyzed prior to TPE (445.38 ng/mL) and ∼10 hours after TPE (51.18 ng/mL), which resulted in an 89% reduction in serum bifenthrin concentration. NEW INFORMATION: TPE may be a promising adjunctive therapeutic modality for bifenthrin toxicosis in dogs.

Marijuana toxicosis in 2 donkeys.

Marijuana toxicosis is typically seen by companion animal veterinarians. However, with increased marijuana availability, there is a greater potential for toxicosis in other species. Herein we describe a case of suspected marijuana toxicosis in a female and a male American Mammoth donkey, aged 8 y and 20 y, respectively, fed cannabis buds. Both cases were presented because of depression and lethargy. However, the jenny had ataxia, mild colic, tachycardia, tachypnea, and decreased tongue tone. Plasma samples from the jenny on presentation and 3 d following hospitalization were submitted to the Kansas State Veterinary Diagnostic Laboratory to be screened for cannabinoids using high-pressure liquid chromatography coupled with tandem mass spectroscopy (HPLC-MS/MS). A single serum sample from the jack was taken on presentation and submitted to the Animal Health Diagnostic Center at Cornell University for Δ9-tetrahydrocannabinol (THC) and cannabidiol analysis using HPLC-MS/MS. THC was detected in all samples. Clinical signs were noted 24-36 h after ingestion, which included mild-to-moderate neurologic deficits, mild colic, tachycardia, tachypnea, and decreased tongue tone. Both donkeys recovered uneventfully within 24 h of peak effects. Utilizing a cannabinoid screening assay in collaboration with a veterinary diagnostic laboratory may be useful when an equine practitioner suspects marijuana toxicosis in a patient.

Long-acting injectable methadone (methadone-fluconazole) provides safe and effective postoperative analgesia in a randomized clinical trial for dogs undergoing soft tissue surgery.

OBJECTIVE: To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia. ANIMALS: 3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included. PROCEDURES: Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale-Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment. RESULTS: Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery. CLINICAL RELEVANCE: Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.

Multiple-dose pharmacokinetics and opioid effects of a novel analgesic with a deterrent to human opioid abuse (methadone-fluconazole-naltrexone) after oral administration in dogs.

OBJECTIVE: To assess the pharmacokinetics and opioid effects of methadone after administration of multiple doses by means of 2 dosing regimens of methadone-fluconazole-naltrexone. ANIMALS: 12 healthy Beagles. PROCEDURES: Dogs were randomly allocated (6 dogs/group) to receive 1 of 2 oral dosing regimens of methadone-fluconazole-naltrexone. Treatment 1 doses were administered at 0 (methadone-to-fluconazole-to-naltrexone ratio of 1:5:0.25 mg/kg), 14 (1:5:0.25), 24 (0.5:2.5:0.125), and 38 (0.5:2.5:0.125) hours. Treatment 2 doses were administered at 0 (1:5:0.25), 4 (0.5:2.5:0.125), 10 (0.5:2.5:0.125), and 24 (0.5:2.5:0.125) hours. Blood samples, rectal temperatures, and von Frey antinociceptive measurements were obtained at designated times. RESULTS: Compared with baseline, temperatures significantly decreased for treatment 1 group dogs at 2 to ≥ 4 hours and from 16 to ≥ 50 hours (12 hours after last dose) and for treatment 2 group dogs at 2 to ≥ 36 hours (12 hours after last dose), when trough methadone concentrations were ≥ 21.3 ng/mL. Antinociception occurred after the first dose but was not maintained throughout the study. Lesions were noted in some dogs at the application site of the von Frey device. Naltrexone and ß-naltrexol were sporadically detected in plasma, and naltrexone glucuronide was consistently detected. CONCLUSIONS AND CLINICAL RELEVANCE: Opioid effects were noted after oral administration of the first dose, and data suggested that administering a second dose 6 hours later and every 12 hours thereafter was necessary to maintain opioid effects. Antinociception may have been lost because dogs became averse or hyperalgesic to the von Frey device, such that the antinociception model used here may not be robust for repeated measurements in dogs.

Detecting and quantifying marijuana metabolites in serum and urine of 19 dogs affected by marijuana toxicity.

Veterinarians diagnose marijuana toxicity based on clinical signs and history, or in conjunction with an over-the-counter (OTC) human urine drug screen. With the legalization of recreational marijuana use becoming more prevalent in the United States, a more accurate test to aid in the diagnosis of canine marijuana toxicity is needed. We collected urine and serum samples from 19 dogs with confirmed or suspected marijuana toxicosis from multiple veterinary hospitals and analyzed them with a novel UPLC-MS/MS method. Calibrations from 0.1 to 100 ng/mL and QC materials were prepared. Samples were extracted, purified, and eluted with solid-phase extraction. Urine samples were tested with an OTC human urine drug screen. The limit of detection (LOD) and lower limit of quantification (LLOQ) ranges for marijuana metabolites in serum were 0.05-0.25 ng/mL and 0.1-0.5 ng/mL, respectively. In urine, the LOD and LLOQ ranges for the metabolites were 0.05-0.1 ng/mL and 0.1-0.5 ng/mL, respectively. In serum, median and range of metabolite concentrations (ng/mL) detected included: THC, 65.0 (0.14-160); 11-OH-Δ9-THC, 4.78 (1.15-17.8); 11-nor-9-carboxy-Δ9-THC, 2.18 (0.71-7.79); CBD, 0.28 (0.11-82.5); and THC-glucuronide, 2.05 (0.72-18.3). In the 19 urine samples, metabolite: creatinine (ng: mg) values detected included: THC, 0.22 (0.05-0.74); 11-OH-Δ9-THC, 0; 11-nor-9-carboxy-Δ9-THC, 1.32 (0.16-11.2); CBD, 0.19 (0.12-0.26); THC-COOH-glucuronide, 0.08 (0.04-0.11); and THC-glucuronide, 0.98 (0.25-10.7). Twenty of 21 urine samples tested negative for THC on the urine drug screen. All 19 serum samples contained quantifiable concentrations of THC using our novel UPLC-MS/MS method. Utilizing a UPLC-MS/MS method can be a useful aid in the diagnosis of marijuana toxicosis in dogs, whereas using an OTC human urine drug test is not a useful test for confirming marijuana exposure in dogs because of the low concentration of THC-COOH in urine.

Perioperative analgesia associated with oral administration of a novel methadone-fluconazole-naltrexone formulation in dogs undergoing routine ovariohysterectomy.

OBJECTIVE: To determine perioperative analgesia associated with oral administration of a novel methadone-fluconazole-naltrexone formulation in dogs undergoing routine ovariohysterectomy. ANIMALS: 43 healthy female dogs. PROCEDURES: Dogs were randomly assigned to receive the methadone-fluconazole-naltrexone formulation at 1 of 2 dosages (0.5 mg/kg, 2.5 mg/kg, and 0.125 mg/kg, respectively, or 1.0 mg/kg, 5.0 mg/kg, and 0.25 mg/kg, respectively, PO, q 12 h, starting the evening before surgery; n = 15 each) or methadone alone (0.5 mg/kg, SC, q 4 h starting the morning of surgery; 13). Dogs were sedated with acepromazine, and anesthesia was induced with propofol and maintained with isoflurane. A standard ovariohysterectomy was performed by experienced surgeons. Sedation and pain severity (determined with the Glasgow Composite Pain Scale-short form [GCPS-SF]) were scored for 48 hours after surgery. Rescue analgesia was to be provided if the GCPS-SF score was > 6. Dogs also received carprofen starting the day after surgery. RESULTS: None of the dogs required rescue analgesia. The highest recorded GCPS-SF score was 4. A significant difference in GCPS-SF score among groups was identified at 6:30 am the day after surgery, but not at any other time. The most common adverse effect was perioperative vomiting, which occurred in 11 of the 43 dogs. CONCLUSIONS AND CLINICAL RELEVANCE: Oral administration of a methadone-fluconazole-naltrexone formulation at either of 2 dosages every 12 hours (3 total doses) was as effective as SC administration of methadone alone every 4 hours (4 total doses) in dogs undergoing routine ovariohysterectomy. Incorporation of naltrexone in the novel formulation may provide a deterrent to human opioid abuse or misuse.