Florfenicol urinary excretion and its potential for treating canine urinary tract infections.

The canine urinary excretion of florfenicol was evaluated to explore its potential for treating urinary tract infections. Nine healthy male intact purpose-bred Beagles and four healthy client-owned dogs each received a single oral dose of florfenicol 20 mg/kg (300 mg/mL parenteral solution) with food. All voluntary urinations were collected for 12 h. Although florfenicol is reportedly bitter tasting, 7/9 Beagles and 4/4 client-owned dogs completely ingested the florfenicol and were enrolled; salivation (n = 1) and headshaking (n = 3) were observed. The last measured urine florfenicol concentrations were variable: Beagles (0.23-3.19 mcg/mL), Pug (3.01 mcg/mL) English Setter (21.29 mcg/mL), Greyhound (32.68 mcg/mL), and Standard Poodle (13.00 mcg/mL). Urine half-life was similar for the Beagles and the Pug, 0.75-1.39 h, whereas the half-life was 1.70-1.82 h for the English Setter, Greyhound, and Standard Poodle. Larger breed dogs exceeded 8 mcg/mL florfenicol (wild-type cutoff) in their urine at 12 h, whereas the Beagles and Pug had <8 mcg/mL; it is unclear if this is an individual, breed, or size difference. These data suggest oral florfenicol may need to be administered q6-12h for canine urinary tract infections, but further data are needed (more enrolled dogs, multiple-dose regimens) before considering clinical trials or breed-specific differences.

Candida auris detected in the oral cavity of a dog in Kansas.

Candida auris is an emerging human fungal pathogen, first described in Japan in 2009, and first detected in the United States in 2016. Here, we report the first-ever description of C. auris colonizing a human pet, the first identification of C. auris in a non-human mammal in the United States and the first C. auris isolate from the state of Kansas. While analyzing the oral mycobiome of dogs from a shelter in Kansas, the oral swab from one dog was found to contain C. auris as well as three other fungal species. The presence of C. auris in a dog suggests the possibility of zoonotic transmission to humans. The isolate is a member of Clade IV, which has been found in patients in Chicago and Florida, while Clades I and III are the most prevalent in the United States. The isolate is resistant to fluconazole, terbinafine, and amphotericin B but susceptible to caspofungin, consistent with the drug-resistant characteristics of many human C. auris isolates. The source of C. auris transient colonization in this dog is unknown, and there is no evidence that it was further transmitted to humans, other dogs in the shelter, or pets in its adopted household. Isolation of C. auris from a dog in Kansas has public health implications as a potential emerging source for the zoonotic spread of this pathogenic fungus, and for the development of antifungal resistance.IMPORTANCECandida auris is an emerging fungal infection of humans and is particularly problematic because it is multi-drug resistant and difficult to treat. It is also known to be spread from person to person by contact and can remain on surfaces for long periods of time. In this report, a dog in a shelter in Kansas is found to be colonized with Candida auris. This is the first study to document the presence of Candida auris on a pet, the first to document C. auris presence on a non-human mammal in the United States, and the first to report an isolate of C. auris within the state of Kansas. The presence of C. auris in a pet dog raises the possibility of zoonotic transmission from pets to human or vice versa.

Correlation of opioid antinociception and hypothermia in dogs-An animal welfare refinement.

The purpose of this study was to assess antinociception and correlation of antinociception and hypothermic effects after intravenous opioids in dogs. Nine healthy male Beagles were enrolled in the study. They were acclimated to a thermal nociceptive device, then received three IV treatments (saline, butorphanol 0.4 mg/kg and methadone 0.5 mg/kg) in a randomized complete block design. Rectal temperature and thermal withdrawals were assessed prior to and 0.5-6 h after drug administration. One dog was excluded due to lack of withdrawal to thermal stimuli. Rectal temperatures were not significantly different between treatments at time 0, but significantly decreased from 0.5 to 5 h for both opioids compared to saline. Withdrawals were significantly decreased, compared to saline, from 0.5 to 4 h for butorphanol and 0.5-5 h for methadone. A significant (p = .0005) and moderate (R2 = .43) correlation between antinociception and hypothermia occurred. Based on these data, intravenous butorphanol (0.4 mg/kg) and methadone (0.5 mg/kg) provided 4 and 5 h of antinociception, respectively. Opioid hypothermia can serve as an easy, noninvasive and humane manner for preclinical assessment of opioid antinociception in dogs prior to evaluation in clinical trials. This is a major refinement in animal welfare for assessing novel opioids, opioid doses and dose intervals in dogs.

Fungal diversity and drug susceptibility of the oral mycobiome of domestic dogs.

The purpose of this study was to characterize the variety and diversity of the oral mycobiome of domestic dogs and to identify the commensal and potentially pathogenic fungi present. Two hundred fifty-one buccal swabs from domestic dogs were obtained and struck onto a chromogenic fungal growth medium that distinguishes between fungal species based on colony color and morphology. After isolating and harvesting single colonies, genomic DNA was extracted from pure cultures. PCR was used to amplify a fungal-specific variable rDNA region of the genome, which was then sent for sequencing. Sequencing results were input into the NCBI BLAST database to identify individual components of the oral mycobiome of tested dogs. Of the 251 dogs swabbed, 73 had cultivable fungi present and 10 dogs had multiple fungal species isolated. Although the dogs did not show signs of oral infections at the time, we did find fungal species that cause pathogenicity in animals and humans. Among fungal isolates, Malassezia pachydermatis and species from the genus Candida were predominant. Following fungal isolate identification, antifungal drug susceptibility tests were performed on each isolate toward the medically important antifungal drugs including fluconazole, ketoconazole, and terbinafine. Drug susceptibility test results indicated that a large number of isolates had high MIC values for all three drugs. Exploring the oral mycobiome of dogs, as well as the corresponding drug susceptibility profiles, can have important implications for canine dental hygiene, health, and medical treatment. Identifying the microorganisms within the canine mouth can illustrate a common pathway for fungal pathogens of One Health concern to spread from our canine companions to humans.

Pharmacokinetic-pharmacodynamic cutoff values for benzylpenicillin in horses to support the establishment of clinical breakpoints for benzylpenicillin antimicrobial susceptibility testing in horses.

Introduction: The aim of this international project was to establish a species-specific Clinical Breakpoint for interpretation of Antimicrobial Susceptibility Testing of benzylpenicillin (BP) in horses. Methods: A population pharmacokinetic model of BP disposition was developed to compute PK/PD cutoff values of BP for different formulations that are commonly used in equine medicine around the world (France, Sweden, USA and Japan). Investigated substances were potassium BP, sodium BP, procaine BP, a combination of procaine BP and benzathine BP and penethamate, a prodrug of BP. Data were collected from 40 horses that provided 63 rich profiles of BP corresponding to a total of 1022 individual BP plasma concentrations. Results: A 3-compartment disposition model was selected. For each of these formulations, the PK/PD cutoff was estimated for different dosage regimens using Monte Carlo simulations. The fAUC/MIC or fT>MIC were calculated with a free BP fraction set at 0.4. For fAUC/MIC, a target value of 72 h (for a 72h treatment) was considered. For fT>MIC, efficacy was assumed when free plasma concentrations were above the explored MIC (0.0625-2 mg/L) for 30 or 40 % of the dosing interval. For continuous infusion, a fT>MIC of 90 % was considered. It was shown that a PK/PD cutoff of 0.25 mg/L can be achieved in 90 % of horses with routine regimen (typically 22,000 IU/kg or 12.4 mg/kg per day) with IM procaine BP once a day (France, Japan, Sweden but not USA1) and with IM sodium BP at 14.07 mg/kg, twice a day or IV sodium BP infusion of 12.4 mg/kg per day. In contrast, penethamate and the combination of procaine BP and benzathine BP were unable to achieve this PK/PD cutoff not even an MIC of 0.125 mg/L. Discussion: The PK/PD cutoff of 0.25 mg/L is one dilution lower than the clinical breakpoint released by the CLSI (0.5 mg/ L). From our simulations, the CLSI clinical breakpoint can be achieved with IM procaine BP twice a day at 22,000 IU i.e. 12.4 mg/kg.

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.

Pharmacokinetics and pharmacodynamics of intramuscular dexmedetomidine in dogs.

OBJECTIVE: To determine the pharmacokinetics and pharmacodynamics of dexmedetomidine after IM administration in dogs. ANIMALS: 6 healthy adult purpose-bred dogs (3 males, 3 females) with a mean ± SD body weight of 25.2 ± 1.8 kg. PROCEDURES: Each dog received 10 µg/kg dexmedetomidine, IM. Heart rate and respiratory rate were counted via cardiac auscultation and visual assessment of chest excursions. Sedation was assessed utilizing 2 sedation scoring systems. Plasma concentrations were determined using ultra performance liquid chromatography-mass spectrometry. Plasma concentrations versus time data after IM dexmedetomidine were analyzed using noncompartmental analysis for extravascular administration. RESULTS: Over the first 2 hours following IM injection of dexmedetomidine, plasma concentrations fluctuated in each dog. The geometric mean (range) maximum plasma concentration was 109.2 (22.4 to 211.5) ng/mL occurring at 20.5 (5 to 75) minutes, and the mean half-life was 25.5 (11.5 to 41.5) minutes. Heart rate was significantly lower than baseline from 30 minutes to 2 hours postdexmedetomidine administration, and respiratory rate was significantly lower than baseline from 45 minutes to 1.75 hours. Dogs were significantly more sedated from 30 minutes to 1.5 hours postdexmedetomidine administration. Median time to onset of sedation was 7.5 minutes (range, 2 to 10 minutes), and median time to peak sedation was 30 minutes (range, 15 to 60 minutes). CLINICAL RELEVANCE: Variations in plasma concentrations occurred in all dogs for the 2 hours postinjection of dexmedetomidine at 10 µg/kg, IM. This was likely due to alterations in absorption due to dexmedetomidine-induced local vasoconstriction. Despite variable plasma concentrations, all dogs were sedated following IM dexmedetomidine administration.

Oral fluconazole has variable pharmacokinetics in dogs.

The purpose of this study was to assess the effects of food and manufacturer on the oral bioavailability of fluconazole in dogs. We hypothesized feeding would decrease fluconazole bioavailability and large variability between manufacturers would occur. Six healthy purpose-bred dogs aged 2-3 years, weighing 9.5-13.7 kg, were enrolled. Each dog was administered a 100 mg fluconazole tablet from three FDA approved manufacturers (1-Glenmark, 2-Citron, 3-Harris) in a randomized crossover block study, fasted for 12 h (fasted) or 15 min after feeding (fed); each dog had 6 treatments. Blood was collected for 72 h after dosing with a 10-day washout between treatments. Fluconazole plasma concentrations were determined with mass spectrometry. Overall variability in dose-normalized drug exposure (AUC/dose) was large (range 1.9-2.9x) within each treatment, while the overall range across all treatments was 3.3-fold. The inter-dog variability in the terminal half-life was also large, 3.1-fold. The mean fed relative oral bioavailability was lower (82%-90%) compared to fasted for each formulation. Due to the large variability, the formulations were not bioequivalent. These data suggest the variability in the half-life was a major contributor to the large variability in fluconazole pharmacokinetics in dogs, while the feeding status and manufacturer were minor contributors.

Dosing protocols to increase the efficacy of butorphanol in dogs.

The purpose of this study was to improve butorphanol dosing in dogs. Twelve Beagles (6 males, 6 females) were enrolled. Six were randomly allocated to each butorphanol treatment: IV (0.4 mg/kg), IV loading dose (0.2 mg/kg) with IV CRI (0.2 mg/kg/h for 8 h), SC (0.4 mg/kg), SC (0.8 mg/kg) with an equal volume sodium bicarbonate (SC-bicarbonate), and IV after CYP inhibitors. We hypothesized that the CRI would produce longer durations than IV bolus, and SC-bicarbonate suspension would produce longer durations than SC. Hypothermia, an opioid effect paralleling antinociception in dogs, and sedation were evaluated. Pharmacokinetics and CYP inhibitor effects on butorphanol pharmacokinetics were determined. Rectal temperatures were significantly lower than baseline from 1.5-4 h (IV), 1-5 h (CRI), and 2-7 h (SC-bicarbonate), but not after SC. Dogs in all treatments had sedation. Butorphanol's half-life was ~1.5 h. SC-bicarbonate had lower bioavailability (61%) relative to SC, with no sustained release, and the CRI mean steady-state plasma concentration was 43.1 ng/ml. CYP inhibitors had minor pharmacokinetic effects on butorphanol. Butorphanol 0.4 mg/kg IV and 0.2 mg/kg loading dose with 0.2 mg/kg/h CRI decreased rectal temperature, but 0.4 mg/kg SC did not. Further studies are required to determine clinical analgesia of butorphanol.

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.

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.

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.

Pseudomonas aeruginosa susceptibility, antibiogram and clinical interpretation, and antimicrobial prescribing behaviors for dogs with otitis in the Midwestern United States.

Pseudomonas aeruginosa (P. aeruginosa) can cause otitis in dogs that is nonresponsive to empirical therapy. This study evaluated P. aeruginosa isolates (N = 216) from canine ear swabs submitted to the Kansas State Veterinary Diagnostic Laboratory from 2018-2020 to create an antibiogram and minimum inhibitory concentration distributions using Clinical Laboratory Standards Institutes breakpoints. Multidrug resistance was defined as non-susceptibility to ≥1 drug from ≥3 antimicrobial classes. Submitting veterinarians (N = 83) were invited to complete a survey about antimicrobial use and otitis management. Susceptibility was higher for aminoglycosides [gentamicin (82%, 177/216) and amikacin (81%, 175/216)] than fluoroquinolones [marbofloxacin (67%, 145/216), enrofloxacin (32%, 70/216), and orbifloxacin (18%, 39/216)]. Most responding veterinarians (54%, 15/28) prescribe topical aminoglycosides as first-line therapy for canine otitis, but 71% (15/21) prescribe fluoroquinolones if rods are seen cytologically. Ceftazidime, imipenem, and piperacillin-tazobactam showed high susceptibility and are used rarely. Multidrug resistance was present in 13% (28/216) of isolates. Based on in vitro susceptibility, topical aminoglycosides might be more effective than fluoroquinolones for P. aeruginosa otitis, but efficacy studies are required. Susceptibility testing is encouraged for cases not responding to empirical therapy but has limitations because topical preparations have high concentrations and otic breakpoints are not available.

Prednisolone and dexamethasone are systemically absorbed after topical application of ophthalmic suspensions in healthy dogs.

OBJECTIVE: To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs. ANIMALS: 12 purpose-bred Beagles. PROCEDURES: Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration. RESULTS: Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone. CLINICAL RELEVANCE: Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.

Plasma concentrations of tramadol after transdermal application of a single metered dose of a compounded tramadol gel to cats.

OBJECTIVE: To determine plasma tramadol concentrations in cats following a single dose of oral and transdermal formulations and the pharmacokinetics for and the concentration of tramadol in the transdermal formulation. ANIMALS: 8 healthy client-owned domestic shorthair cats. PROCEDURES: 1 cat was orally administered 1 dose of tramadol (2 mg/kg), and 7 cats received 1 dose of a proprietary compounded tramadol gel product (median actual dose, 2.8 mg/kg) applied to their inner pinnae. Plasma tramadol concentrations were measured with high-performance liquid chromatography-mass spectrometry at fixed times over 24 hours. RESULTS: Plasma tramadol concentrations were undetectable or much lower (range, < 1 to 4.3 ng/mL) following application of the transdermal formulation, compared with those following oral administration (maximum plasma tramadol concentration, 261.3 ng/mL [at 4 hours]). Tramadol pharmacokinetics for the transdermal formulation could not be determined. Tramadol concentrations of the transdermal gel product exceeded the estimated label dose in all analyzed gel samples, with concentrations greater than the 90% to 110% United States Pharmacopeia standard for compounded drugs. CONCLUSIONS AND CLINICAL RELEVANCE: Application of 1 dose of the proprietary transdermal formulation did not yield clinically relevant plasma tramadol concentrations in cats. Although this proprietary formulation is currently available to prescribing veterinarians, it should be used with caution.

Comparisons of hematologic results for juvenile versus adult shelter dogs presented for ovariohysterectomy or castration.

OBJECTIVE: To compare hematologic results for juvenile versus adult dogs from shelters that outwardly appeared healthy and were presented for ovariohysterectomy or castration. ANIMALS: 138 dogs from 13 regional shelters. PROCEDURES: Each dog underwent a physical examination (including use of a flea comb), age estimation by dental eruption characteristics, PCV, CBC, and tests for Dirofilaria immitis antigen and Anaplasma phagocytophilum, Borrelia burgdorferi, and Ehrlichia canis antibodies. Additional diagnostic tests were performed as needed. Dogs were grouped by age as < 3, ≥ 3 to ≤ 6, or > 6 months of age, with dogs ≤ 6 months of age considered juveniles and dogs > 6 months of age considered adults. Hematologic results were compared across groups. RESULTS: There were 138 dogs, of which 56 were juveniles (34 dogs < 3 months old; 22 dogs ≥ 3 to ≤ 6 months old) and 82 were adults. Juvenile (vs adult) dogs had lower mean calculated Hct and mean PCV whether dogs with infectious agents or parasites were included or excluded. The mean PCV and mean cell hemoglobin concentration were lower and the reticulocyte count higher for juvenile dogs < 3 months old (35.8%, 33.1 g/dL, and 135,000 reticulocytes/µL) versus adults (44.9%, 34.7 g/dL, and 68,500 reticulocytes/µL). Most (98.6%) dogs underwent surgery as scheduled; 2 dogs had surgery postponed because of thrombocytopenia or parvovirus infection. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings indicated that outwardly healthy-appearing juvenile shelter dogs often have results for PCV and calculated Hct that are lower than those for adult shelter dogs and adult dog reference intervals but rarely require postponement of ovariohysterectomy or castration.

TERBINAFINE PHARMACOKINETICS FOLLOWING SINGLE-DOSE ORAL ADMINISTRATION IN RED-EARED SLIDER TURTLES (TRACHEMYS SCRIPTA ELEGANS): A PILOT STUDY.

In this pilot study, the pharmacokinetics of terbinafine were determined in six apparently healthy red-eared slider turtles (Trachemys scripta elegans) after a single PO administration. Terbinafine suspension (15 mg/kg, once) was administered via gavage tube to all turtles. Blood samples were collected immediately before (time 0) and at 1, 2, 4, 8, 24, and 48 h after drug administration. Plasma terbinafine concentrations were quantified by ultra-performance liquid chromatography-mass spectrometry, and noncompartmental pharmacokinetic analysis was performed. None of the animals showed any adverse responses following terbinafine administration. Mean area under the curve from time 0 to 24 h was 1,213 h × ng/ml (range 319-7,309), mean peak plasma concentration was 201.5 ng/ml (range 45.8-585.3), mean time to maximum plasma concentration was 1.26 h (range 1-4), mean residence time was 7.71 h (range 3.85-14.8), and mean terminal half-life was 5.35 h (range 2.67-9.83). The administration of terbinafine (15 mg/kg, PO) may be appropriate for treatment of select fungal organisms with low minimum inhibitory concentrations in red-eared slider turtles but may require q12h administration even for organisms with low minimum inhibitory concentrations. Multiple-dose studies as well as clinical studies are needed to determine ideal dosages and efficacy.

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.

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.

Evaluation of urine concentrations of amoxicillin and clavulanate in cats.

BACKGROUND: To characterize urinary isolates, the Clinical and Laboratory Standards Institute (CLSI) uses an amoxicillin breakpoint for cats based on plasma (not urine) drug concentrations (≤0.25 µg/mL), but a urine-specific breakpoint for dogs exists (≤8 µg/mL). OBJECTIVES: To measure urine concentrations of amoxicillin and clavulanate after PO administration of amoxicillin-clavulanate to cats, and to suggest updated urine-specific susceptibility breakpoints for PO amoxicillin and amoxicillin-clavulanate in cats. ANIMALS: Eleven healthy purpose-bred cats. METHODS: Cats were given 3 62.5 mg doses of amoxicillin-clavulanate PO q12h. After the third dose, urine was collected over 28 hours, recording urination time and volume. At least 3 urine samples were collected per cat. Liquid chromatography with mass spectrometry was used to determine the urine concentrations of amoxicillin and clavulanate. RESULTS: Amoxicillin concentrations were >8 µg/mL in all urine samples collected within 12 hours after administration (range, 31.6-1351 µg/mL), with means of 929 µg/mL (0-6 hours) and 532 µg/mL (6-12 hours). The mean half-life of amoxicillin in urine was 1.99 hours, and mean recovery was 30%. Clavulanate was detected in all urine samples, with mean half-life of 2.17 hours. CONCLUSIONS AND CLINICAL IMPORTANCE: Orally administered amoxicillin-clavulanate resulted in urine amoxicillin concentrations above the cutoff (8 µg/mL) for wild-type Escherichia coli in all cats. Because urine-specific susceptibility testing breakpoints can be determined using urine concentrations, this information should allow new CLSI uropathogen susceptibility breakpoints for amoxicillin and amoxicillin-clavulanate in healthy cats, increasing the urine breakpoint from ≤0.25 to ≤8 µg/mL.