Clinical features of tularemia in cats: a retrospective study from 2000 to 2021.

OBJECTIVES: The objectives of this study were to describe the clinical features of cats diagnosed with tularemia, and to compare the clinical features of cats with and without tularemia and identify characteristics increasing the likelihood of a tularemia diagnosis. METHODS: Diagnostic laboratory data and medical records were retrospectively reviewed of cats tested for tularemia between 2000 and 2021. Clinical features including signalment, presenting complaint(s), physical examination findings and clinicopathologic data were described for cats with tularemia diagnosed by culture and/or PCR. Clinical features were also compared between PCR+ vs PCR- cats and logistic regression was used to identify features that predicted PCR+ status. RESULTS: A total of 18 cats were diagnosed with tularemia. The affected cats had a mean age of 5.8 ± 4.9 years, with a slight male predominance. Most were domestic shorthair cats and had outdoor access. Common presenting complaints included lethargy and anorexia, while physical examination findings frequently revealed fever, peripheral lymphadenomegaly and oral ulcers. Laboratory findings varied, with notable abnormalities including neutrophilic inflammation observed on cytology and widespread acute systemic pathologic changes in necropsy results. Leukopenia and neutropenia were more common in PCR+ vs PCR- cats, and these factors were 7.4 times (confidence interval [CI] 1.2-62.3) and 10.0 times (CI 1.4-83.2) more likely to occur in PCR+ vs PCR- cats, respectively. There were no significant differences between the groups in other parameters including anemia, thrombocytopenia, band neutrophilia and hyperbilirubinemia. CONCLUSIONS AND RELEVANCE: This study provides a more comprehensive description of tularemia in cats than has been available to date. In particular, leukopenia and neutropenia are significantly associated with tularemia-positive cats. These clinical features should be considered and raise suspicion for tularemia in cats. These findings may be valuable for the timely diagnosis, treatment and prevention of tularemia outbreaks in cats and humans.

Digital Immunoassay for Rapid Detection of SARS-CoV-2 Infection in a Broad Spectrum of Animals.

The ability of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) to infect a wide-range of species raises significant concerns regarding both human-to-animal and animal-to-human transmission. There is an increasing demand for highly sensitive, rapid, and simple diagnostic assays that can detect viral infection across various species. In this study, we developed a biosensor assay that adapted a monoclonal-antibody (mAb)-based blocking ELISA format into an Activate Capture + Digital Counting (AC + DC)-based immunoassay. The assay employs a photonic crystal (PC) biosensor, gold-nanoparticle (AuNP) tags, SARS-CoV-2 nucleocapsid (N) protein, and specific anti-N mAb to detect antibody responses in animals exposed with SARS-CoV-2. We demonstrated a simple 2-step 15-min test that was capable of detecting as low as 12.5 ng of antibody in controlled standard serum samples. Based on an evaluation of 176 cat serum samples with known antibody status, an optimal percentage of inhibition (PI) cut-off value of 0.588 resulted in a diagnostic sensitivity of 98.3% and a diagnostic specificity of 96.5%. The test is highly repeatable with low variation coefficients of 2.04%, 2.73%, and 4.87% across different runs, within a single run, and on a single chip, respectively. The test was further employed to detect antibody responses in multiple animal species as well as investigate dynamics of antibody response in experimentally infected cats. This test platform provides an important tool for rapid field surveillance of SARS-CoV-2 infection across multiple species.

Assessing Illinois companion animal veterinarians' antimicrobial prescription practices and the factors that influence their decisions when treating bacterial infections in dogs and cats.

AIMS: Judicious antimicrobial use in companion animal practice is critical for maintaining the effectiveness of antimicrobial agents against bacterial infections and reducing the selection of antimicrobial-resistant bacteria. This study aimed to provide insights into companion animal veterinarians' antimicrobial treatment recommendations for common bacterial infections in dogs and cats and describe the factors influencing their prescription choices. METHODS AND RESULTS: An online survey using QualtricsXM® software was administered between September and November 2022 to companion animal veterinarians who were Illinois State Veterinary Medical Association members. Descriptive and text analyses were conducted to assess the participants' responses. A total of 78 surveys were included in the analysis. Skin infections were ranked as the most common bacterial infections for which veterinarians prescribed antimicrobial agents, followed by ear, urinary tract, respiratory, and enteric infections. The severity of clinical symptoms and the results of bacterial culture and susceptibility tests were the most influential factors for veterinarians when making antimicrobial prescription choices. Veterinarians were aware of the current antimicrobial prescription guideline recommendations when prescribing antimicrobials empirically to nine hypothetical scenarios of bacterial infections. According to the results of the text analysis that assessed veterinarians' responses to an open-ended question, regarding their challenges when prescribing antimicrobial agents, the pairwise correlation of word frequencies within each response showed the highest correlations between the words 'owner' and 'compliance', 'administration' and 'route', 'cost' and 'culture', and 'patients' and 'acceptance'. CONCLUSIONS: The study results can support animal health stakeholders in the development of antimicrobial stewardship programmes to promote appropriate antimicrobial use and limit the emergence of antimicrobial resistance.

Case series of dogs with blastomycosis managed with high-flow nasal oxygen therapy (2019-2023): 19 cases.

Objective: To describe the clinical presentation, progression, treatment, and outcome of dogs with blastomycosis treated with high-flow nasal oxygen therapy (HFNOT). Design: Retrospective case review. Setting: University veterinary teaching hospital. Animals: Nineteen client-owned dogs with strongly suspected or confirmed blastomycosis treated with HFNOT. Measurements and main results: The medical records of dogs with strongly suspected or confirmed blastomycosis between October 2019 and May 2023 that received HFNOT were evaluated. Nineteen dogs were included. Nine dogs were started directly on high-flow nasal oxygen therapy. The remaining 10 dogs first received traditional oxygen therapy and were then transitioned to HFNOT 3-142 h later. Of the 19 dogs, 1 survived to discharge from hospital, 12 were euthanized due to progression of disease, and 6 died during the hospitalization period. Conclusions and clinical importance: The prognosis for survival of dogs with severe blastomycosis requiring therapy beyond traditional oxygen methods was poor to grave in this population. This is the first known documented report of HFNOT use in dogs with confirmed or suspected blastomycosis.

Spatial and temporal clustering of anti-SARS-CoV-2 antibodies in Illinois household cats, 2021-2023.

This study aimed to evaluate the seroprevalence and spatial and temporal clustering of SARS-CoV-2 antibodies in household cats within 63 counties in Illinois from October 2021 to May 2023. The analysis followed a stepwise approach. First, in a choropleth point map, we illustrated the distribution of county-level seroprevalence of SARS-CoV-2 antibodies. Next, spatial interpolation was used to predict the seroprevalence in counties without recorded data. Global and local clustering methods were used to identify the extent of clustering and the counties with high or low seroprevalence, respectively. Next, temporal, spatial, and space-time scan statistic was used to identify periods and counties with higher-than-expected seroprevalence. In the last step, to identify more distinct areas in counties with high seroprevalence, city-level analysis was conducted to identify temporal and space-time clusters. Among 1,715 samples tested by serological assays, 244 samples (14%) tested positive. Young cats had higher seropositivity than older cats, and the third quarter of the year had the highest odds of seropositivity. Three county-level space-time clusters with higher-than-expected seroprevalence were identified in the northeastern, central-east, and southwest regions of Illinois, occurring between June and October 2022. In the city-level analysis, 2 space-time clusters were identified in Chicago's downtown and the southwestern suburbs of Chicago between June and September 2022. Our results suggest that the high density of humans and cats in large cities such as Chicago, might play a role in the transmission and clustering of SARS-CoV-2. Our study provides an in-depth analysis of SARS-CoV-2 epidemiology in Illinois household cats, which will aid in COVID-19 control and prevention.

Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid protein. To detect SARS-CoV-2 antibodies in a broad spectrum of animal species, an mAb-based blocking enzyme-linked immunosorbent assay (bELISA) was developed. Test validation using a set of animal serum samples with known infection status obtained an optimal percentage of inhibition cut-off value of 17.6% with diagnostic sensitivity of 97.8% and diagnostic specificity of 98.9%. The assay demonstrates high repeatability as determined by a low coefficient of variation (7.23%, 4.89%, and 3.16%) between-runs, within-run, and within-plate, respectively. Testing of samples collected over time from experimentally infected cats showed that the bELISA was able to detect seroconversion as early as 7 days post-infection. Subsequently, the bELISA was applied for testing pet animals with coronavirus disease 2019 (COVID-19)-like symptoms and specific antibody responses were detected in two dogs. The panel of mAbs generated in this study provides a valuable tool for SARS-CoV-2 diagnostics and research. The mAb-based bELISA provides a serological test in aid of COVID-19 surveillance in animals. IMPORTANCE Antibody tests are commonly used as a diagnostic tool for detecting host immune response following infection. Serology (antibody) tests complement nucleic acid assays by providing a history of virus exposure, no matter symptoms developed from infection or the infection was asymptomatic. Serology tests for COVID-19 are in high demand, especially when the vaccines become available. They are important to determine the prevalence of the viral infection in a population and identify individuals who have been infected or vaccinated. ELISA is a simple and practically reliable serological test, which allows high-throughput implementation in surveillance studies. Several COVID-19 ELISA kits are available. However, they are mostly designed for human samples and species-specific secondary antibody is required for indirect ELISA format. This paper describes the development of an all species applicable monoclonal antibody (mAb)-based blocking ELISA to facilitate the detection and surveillance of COVID-19 in animals.

Assessing the urinary concentration of nitrofurantoin and its antibacterial activity against Escherichia coli, Staphylococcus pseudintermedius, and Enterococcus faecium isolated from dogs with urinary tract infections.

Nitrofurantoin, a broad-spectrum nitrofuran class antibiotic, is applied as a first-line antibiotic in treating human urinary tract infections (UTIs) due to its great efficacy and high achievable concentration. The interest in using this antibiotic in companion animals has increased due to the growing demand for effective antibiotics to treat UTIs caused by multidrug-resistant bacteria. Currently, the susceptibility interpretations for nitrofurantoin are based on the breakpoints set for humans, while the canine-specific breakpoints are still unavailable. In this study, we assessed the concentration of nitrofurantoin reaching the dog's urine using the recommended oral dosing regimen. In addition, we examined the efficacy of this breakpoint concentration against the common canine UTI pathogens, Escherichia coli, Staphylococcus pseudintermedius, and Enterococcus faecium. Eight experimental beagle dogs were treated with ~5 mg/kg of nitrofurantoin macrocrystal PO 8qh for 7 days. The urine samples were collected via cystocentesis at 2, 4, and 6 h after administration on day 2 and day 7 and used to quantify nitrofurantoin concentrations by ultra-high performance liquid chromatography. The results showed that 26.13-315.87 µg/mL nitrofurantoin was detected in the dogs' urine with a mean and median concentration of 104.82 and 92.75 µg/mL, respectively. Additionally, individual dogs presented with urinary nitrofurantoin concentrations greater than 64 µg/mL for at least 50% of the dosing intervals. This concentration efficiently killed E. coli, and S. pseudintermedius, but not E. faecium strains carrying an MIC90 value equal to 16, 16, and 128 µg/mL, respectively. Taken together, these results suggest that the value of 64 µg/mL may be set as a breakpoint against UTI pathogens, and nitrofurantoin could be an effective therapeutic drug against E. coli and S. pseudintermedius for canine UTIs.

Pharmacokinetic, sedative, and physiological effects of oral compounded formulations of trazodone alone or in combination with gabapentin in male cats.

Trazodone and gabapentin are common oral sedatives in cats, used alone or combined, but no pharmacokinetic studies exist for trazodone in this species. The objective of this study was to determine the pharmacokinetics of oral trazodone (T) alone, or in combination with gabapentin (G) in healthy cats. Cats (n = 6) were randomly allocated to receive T (3 mg/kg) intravenously (IV), T (5 mg/kg) orally (PO), or T (5 mg/kg) and G (10 mg/kg) PO with a 1-week washout period between treatments. Heart rate, respiratory rate, indirect blood pressure, and level of sedation were assessed, and venous blood samples were collected serially over 24 h. Analysis of plasma trazodone concentration was performed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral T administration resulted in a bioavailability of 54.9(7-96)%, and 17.2(11-25)% when administered with G. Tmax 0.17 (0.17-0.5) and 0.17 (0.17-0.75) h; Cmax 1.67 ± 0.91 and 1.22 ± 0.54 µg/mL, AUC 5.23 (2.0-18.76) and 2.37 (1.17-7.80) h*µg/mL; T1/2 5.12 ± 2.56 and 4.71 ± 1.07 h; for T and TG, respectively. Sedation was significant when compared to baseline in all groups from 20 or 45 min to 8 h indicating some lag between peak plasma concentration and sedative effects. Physiological variables remained within normal limits. This study concludes that oral trazodone is rapidly absorbed in healthy cats. Addition of gabapentin did not result in more profound sedation, showing no clinical advantage of combining these drugs in this study population.

Evaluating the clinical utility of the systemic inflammatory response syndrome criteria in dogs and cats presenting to an emergency department.

OBJECTIVE: Evaluate the clinical utility of the systemic inflammatory response syndrome (SIRS) criteria in dogs and cats presenting to an emergency room (ER). DESIGN: Prospective and retrospective observational study, conducted from November 2019 to February 2020. SETTING: Small animal university teaching hospital. ANIMALS: Prospective enrollment of 1143 dogs and 384 cats consecutively presenting to the ER. Retrospective enrollment of 65 healthy dogs and 57 healthy cats consecutively presenting to the primary care (PC) service. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Positive SIRS-3 status was defined as meeting ≥2 of 3 (dogs) or 3 of 3 (cats) of the vital parameter SIRS criteria (temperature, heart rate, and respiratory rate). Positive SIRS-4 status was defined as meeting ≥2 of 4 (dogs) and ≥3 of 4 (cats) of the vital parameter and CBC SIRS criteria. For each species, proportions of SIRS-positive animals were compared between the ER and PC groups. Clinical outcomes were compared between SIRS-positive and SIRS-negative patients presenting to ER. The number of SIRS-3-positive dogs was statistically but not clinically different between the ER (69.9%) and PC (53.8%) groups (P = 0.009). Overall survival rate was 83% for SIRS-3-positive and 89% for SIRS-3-negative dogs presented to ER (P = 0.007). The number of SIRS-3-positive cats did not differ between ER and PC groups (P > 0.999). Overall survival rate was 61.1% for SIRS-4-positive and 86.8% for SIRS-4-negative cats presented to ER (P = 0.012). CONCLUSIONS: Fulfilling the SIRS criteria is common in dogs and rare in cats regardless of presenting service. Meeting SIRS criteria on ER presentation carries a weak negative survival association in dogs and a moderate negative survival association in cats. This study demonstrates that the SIRS criteria have poor discriminatory ability to differentiate healthy from diseased patients and lacks a strong outcome correlation in small animal patients.

Development of monoclonal antibody-based blocking ELISA for detecting SARS-CoV-2 exposure in animals.

The global pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a significant threat to public health. Besides humans, SARS-CoV-2 can infect several animal species. Highly sensitive and specific diagnostic reagents and assays are urgently needed for rapid detection and implementation of strategies for prevention and control of the infection in animals. In this study, we initially developed a panel of monoclonal antibodies (mAbs) against SARS-CoV-2 nucleocapsid (N) protein. To detect SARS-CoV-2 antibodies in a broad spectrum of animal species, a mAb-based bELISA was developed. Test validation using a set of animal serum samples with known infection status obtained an optimal percentage of inhibition (PI) cut-off value of 17.6% with diagnostic sensitivity of 97.8% and diagnostic specificity of 98.9%. The assay demonstrates high repeatability as determined by a low coefficient of variation (7.23%, 6.95%, and 5.15%) between-runs, within-run, and within-plate, respectively. Testing of samples collected over time from experimentally infected cats showed that the bELISA was able to detect seroconversion as early as 7 days post-infection. Subsequently, the bELISA was applied for testing pet animals with COVID-19-like symptoms and specific antibody responses were detected in two dogs. The panel of mAbs generated in this study provides a valuable tool for SARS-CoV-2 diagnostics and research. The mAb-based bELISA provides a serological test in aid of COVID-19 surveillance in animals. IMPORTANCE: Antibody tests are commonly used as a diagnostic tool for detecting host immune response following infection. Serology (antibody) tests complement nucleic acid assays by providing a history of virus exposure, no matter symptoms developed from infection or the infection was asymptomatic. Serology tests for COVID-19 are in high demand, especially when the vaccines become available. They are important to determine the prevalence of the viral infection in a population and identify individuals who have been infected or vaccinated. ELISA is a simple and practically reliable serological test, which allows high-throughput implementation in surveillance studies. Several COVID-19 ELISA kits are available. However, they are mostly designed for human samples and species-specific secondary antibody is required for indirect ELISA format. This paper describes the development of an all species applicable monoclonal antibody (mAb)-based blocking ELISA to facilitate the detection and surveillance of COVID-19 in animals.

The pharmacokinetics of single oral dose extended-release topiramate and adverse effects after multi-dose administration in healthy cats.

Current treatment options for feline epilepsy are limited to medications that require administration of multiple doses per day or administration of a capsule or large tablet. Expanding the current treatment options could improve patient and owner compliance and optimize seizure control. Topiramate has been used sparingly in veterinary medicine, and limited pharmacokinetic studies have focused on immediate release formulations in dogs. If effective and safe, topiramate extended-release (XR) could broaden the current treatment options for feline epilepsy. The aims of this two-phase study were to establish single-dose pharmacokinetics for topiramate XR in cats, identify a dosing regimen that maintains steady-state plasma drug concentrations within a reference range extrapolated from human medicine (5-20 µg/mL), and evaluate the safety of topiramate XR in cats following multidose administration. Topiramate XR administered orally at 10 mg/kg once daily for 30 days was sufficient to achieve the desired concentrations in all cats. While no clinically apparent adverse effects were observed, four out of eight cats developed subclinical anemia, calling into question the safety of topiramate XR with chronic administration. Further studies are necessary to better understand the potential adverse effects and overall efficacy of topiramate XR for the treatment of feline epilepsy.

The Future of Diabetes Therapies: New Insulins and Insulin Delivery Systems, Glucagon-Like Peptide 1 Analogs, Sodium-Glucose Cotransporter Type 2 Inhibitors, and Beta Cell Replacement Therapy.

As the prevalence of diabetes mellitus increases, so too does the number of available treatment modalities. Many diabetic therapies available in human medicine or on the horizon could hold promise in the management of small animal diabetes. However, it is important to consider how species differences in pathophysiology, management practices and goals, and lifestyle may affect the translation of such treatment modalities for veterinary use. This review article aimed to familiarize veterinarians with the more promising novel diabetic therapies and explore their possible applications in the treatment of canine and feline diabetes mellitus.

Single-dose pharmacokinetics of telmisartan oral solution and effect of feeding in dogs.

Telmisartan is an angiotensin II receptor blocker that has great potential to improve the treatment of hypertension, proteinuria, and cardiovascular disease in dogs. A feline-approved telmisartan oral solution (TOS) is available, but this formulation has not been evaluated in dogs. The aims of this study were to establish the pharmacokinetics of telmisartan administered as TOS and determine the effect of feeding on drug absorption in dogs. In a cross-over design, seven healthy dogs received 1 mg/kg telmisartan orally as TOS with or without food and underwent serial measurement of plasma telmisartan concentrations over 24 h. Bioequivalence of TOS administered with vs. without food was assessed by the 90% confidence interval method for maximum concentration (Cmax ), and the observed and extrapolated areas under the curve (AUC0-t and AUC0-∞ ). The mean ratios of these parameters were 0.97 (CI 0.74-1.27), 0.92 (0.81-1.03), and 0.90 (0.82-1.00), respectively. Feeding methods were not bioequivalent based on Cmax due to interindividual variation. These results suggest that TOS can be given to dogs with or without food but should be administered in the same way consistently. Additional pharmacokinetic and pharmacodynamic studies are warranted to confirm this recommendation and establish the therapeutic targets for telmisartan in dogs.

Bioencapsulation is a feasible method of terbinafine administration in Emydomyces testavorans-infected western pond turtles (Actinemys marmorata).

OBJECTIVE: To evaluate the pharmacokinetics of terbinafine administered to western pond turtles (Actinemys marmorata) via oral gavage and bioencapsulated in earthworms. ANIMALS: 7 western pond turtles. PROCEDURES: A randomized complete crossover single-dose pharmacokinetic study was performed. Compounded terbinafine (25 mg/mL; 30 mg/kg) was administered through oral gavage (OG) directly into the stomach or bioencapsulated (BEC) into an earthworm vehicle. Blood (0.2 mL) was drawn from the jugular vein at 0, 0.5, 1, 2, 4, 8, 12, 24, 48, 72, and 120 hours after administration. Plasma terbinafine levels were measured using high-performance liquid chromatography. RESULTS: Peak plasma terbinafine concentrations of 786.9 ± 911 ng/mL and 1,022.2 ± 911 were measured at 1.8 ± 2.8 and 14.1 ± 12.3 hours after OG and BEC administration, respectively. There was a significant (P = .031) increase in area under the curve with BEC compared to OG. Using steady-state predictions, with once-daily terbinafine administration, 3/7 and 7/7 turtles had plasma concentrations persistently greater than the minimum inhibitory concentration (MIC) for Emydomyces testavorans for the OG and BEC administration routes of administration, respectively. With administration every 48 hours, 3/7 turtles for the OG phase and 6/7 turtles for the BEC phase had concentrations greater than the E. testavorans MIC throughout the entire dosing interval. CLINICAL RELEVANCE: Administration of terbinafine (30 mg/kg) every 24 or 48 hours via earthworm bioencapsulation in western pond turtles may be appropriate for the treatment of shell lesions caused by E. testavorans. Clinical studies are needed to assess the efficacy of treatment.

Longitudinal analysis of the rectal microbiome in dogs with diabetes mellitus after initiation of insulin therapy.

There have been numerous studies in humans and rodents substantiating the role of the gastrointestinal microbiome in the pathogenesis and progression of both type 1 and type 2 diabetes mellitus. Diabetes mellitus is a common endocrinopathy in dogs; however, little is known about the composition of the gut microbiome during the development and treatment of diabetes in this species. The objective of this pilot study was to characterize the gastrointestinal microbiome of dogs with diabetes mellitus at the time of diagnosis and over the first 12 weeks of insulin therapy and identify associations with glycemic control. Rectal swabs and serum for fructosamine measurement were collected from 6 newly diagnosed diabetic dogs at 2-week intervals for 12 weeks. Rectal samples were sequenced using 16S, ITS, and archaeal primers. Measures of alpha and beta diversity were assessed for changes over time; associations between absolute sequence variant (ASV) relative abundances and time and fructosamine concentration were identified using a microbiome-specific, multivariate linear effects model. No statistically significant changes over time were noted in alpha diversity and samples significantly grouped by dog rather than by time in the beta diversity analysis. However, multiple ASVs were negatively (Clostridium sensu stricto 1, Romboutsia, Collinsella) and positively (Streptococcus, Bacteroides, Ruminococcus gauveauii, Peptoclostridium) associated with time and two ASVs were positively associated with fructosamine (Enterococcus, Escherichia-Shigella). These changes in gastrointestinal microbial composition warrant further investigation of how they may relate to diabetes mellitus progression or control in dogs.

Cytochrome P450 reaction phenotyping of itraconazole hydroxylation in the dog.

Itraconazole (ITZ) is an important drug in the treatment of superficial and deep mycoses in dogs. Its primary metabolite is hydroxy-itraconazole, which has antifungal activity similar to the parent compound. The purpose of this study was to identify the cytochrome P450 enzyme (CYP) isoform(s) responsible for ITZ hydroxylation in canine liver. Reaction kinetics for ITZ hydroxylation were determined in a panel of canine recombinant CYPs and dog liver microsomes (DLMs). Findings were confirmed using CYP isoform-specific inhibitors in rCYPs and DLMs. In rCYP experiments, CYP2D15 and CYP3A12 had highest activity for ITZ hydroxylation. In inhibitor experiments, quinidine and erythromycin inhibited ITZ hydroxylation in CYP2D15 and CYP3A12, respectively, in an isoform-specific manner. In DLMs, quinidine and erythromycin combined inhibited ITZ hydroxylation more than erythromycin alone but not quinidine alone. However, this may be related to inhibitor potency rather than the contribution of the individual CYP isoforms to the reaction. These findings support a role for CYP2D15 and CYP3A12 in ITZ biotransformation in canine liver.

Pharmacokinetics of a 503B outsourcing facility-produced theophylline in dogs.

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 µg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 µg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.

Single-dose pharmacokinetics of orally administered terbinafine in bearded dragons (Pogona vitticeps) and the antifungal susceptibility patterns of Nannizziopsis guarroi.

OBJECTIVE: To identify the antifungal susceptibility of Nanniziopsis guarroi isolates and to evaluate the single-dose pharmacokinetics of orally administered terbinafine in bearded dragons. ANIMALS: 8 healthy adult bearded dragons. PROCEDURES: 4 isolates of N guarroi were tested for antifungal susceptibility. A compounded oral solution of terbinafine (25 mg/mL [20 mg/kg]) was given before blood (0.2 mL) was drawn from the ventral tail vein at 0, 4, 8, 12, 24, 48, 72, and 96 hours after administration. Plasma terbinafine concentrations were measured with high-performance liquid chromatography. RESULTS: The antifungal minimum inhibitory concentrations against N guarroi isolates ranged from 4,000 to > 64,000 ng/mL for fluconazole, 125 to 2,000 ng/mL for itraconazole, 125 to 2,000 ng/mL for ketoconazole, 125 to 1,000 ng/mL for posaconazole, 60 to 250 ng/mL for voriconazole, and 15 to 30 ng/mL for terbinafine. The mean ± SD peak plasma terbinafine concentration in bearded dragons was 435 ± 338 ng/mL at 13 ± 4.66 hours after administration. Plasma concentrations remained > 30 ng/mL for > 24 hours in all bearded dragons and for > 48 hours in 6 of 8 bearded dragons. Mean ± SD terminal half-life following oral administration was 21.2 ± 12.40 hours. CLINICAL RELEVANCE: Antifungal susceptibility data are available for use in clinical decision making. Results indicated that administration of terbinafine (20 mg/kg, PO, q 24 to 48 h) in bearded dragons may be appropriate for the treatment of dermatomycoses caused by N guarroi. Clinical studies are needed to determine the efficacy of such treatment.

Pharmacokinetics of thiamine (vitamin B1) in adult horses after administration of three single intravenous doses.

Thiamine is a vital co-factor for several anti-inflammatory and antioxidant processes that are critical for mitigation of sepsis-associated inflammation, but pharmacokinetic (PK) analysis has not been reported in horses. We hypothesized that IV thiamine hydrochloride (TH) at increasing dosages would result in corresponding increases in plasma thiamine concentrations without causing adverse effects. A randomized cross-over study was performed in 9 healthy horses that each received TH at 5, 10, and 20 mg/kg IV. Blood was collected immediately prior to drug administration and at several time points thereafter. High-performance liquid chromatography with mass spectrometry was used to quantify thiamine concentrations at each time point. Non-compartmental PK methods showed that IV TH resulted in supraphysiologic plasma concentrations with a short half-life (0.77-1.12 h) and no adverse clinical signs were observed. The terminal rate constant decreased as the dosage increased (p < .0001) and clearance significantly decreased at the 20 mg/kg dosage (p = .0011). The area under the curve (AUC) increased in a non-linear fashion. These findings suggest that thiamine follows non-linear elimination kinetics in horses, which is likely due to saturation of renal elimination. Future studies are needed to identify therapeutic plasma concentrations and develop thiamine dosing recommendations for horses.

Pharmacokinetics of a cytosine arabinoside subcutaneous protocol in dogs with meningoencephalomyelitis of unknown aetiology.

Cytosine arabinoside (CA) is a commonly used treatment for dogs with meningoencephalomyelitis of unknown aetiology (MUE) with various proposed protocols, many requiring 24 hours (h) of hospitalization or two visits within 24 h. This is a unidirectional study evaluating the pharmacokinetics of a CA subcutaneous (SC) protocol and a standard constant rate infusion (CRI) protocol in 8 dogs with MUE. Dogs received the CRI (200 mg/m2 IV over 24 h), followed by a SC protocol (50 mg/m2 every 2 h for 4 treatments) four weeks later. Plasma CA concentrations were measured by high-pressure liquid chromatography-tandem mass spectrometry (HPLC-MS). Median peak CA concentration for the SC protocol (3.40 µg/ml, range 1.60-9.70 µg/ml) was significantly higher than the CRI (1.09 µg/ml, range 0.77-1.67 µg/ml; p = .02). Median concentration at 1h and 8h following initiation of treatment was significantly higher for the SC protocol (CA1 2.28 µg/ml, range 0.97-2.67; CA8 1.83 µg/ml, range 0.77-2.84) compared to the CRI (CA1 0.01 µg/ml, range 0-0.45; CA8 0.74 µg/ml, range 0.67-1.11; p = .01). While the PK properties of CA when administered as a CRI has been previously investigated, this study demonstrated that CA when administered via repeated 50 mg/m2 injections every 2 h over an 8-h period, provided sustained plasma levels above its therapeutic target and for a significantly longer duration of time than did a standard CRI protocol.