PREVALENCE OF THE ABCB1-1Δ GENE IN NONDOMESTIC SPECIES OF THE CANIDAE FAMILY.

The ABCB1 gene is responsible for encoding the P-glycoprotein (P-gp) efflux transporter that prevents accumulation of exogenous substances in the body by utilizing ATP hydrolysis to transport these substances against their concentration gradient. In dogs, homozygous or heterozygous mutations for the previously described ABCB1-1Δ mutation lead to ineffective P-gp efflux transport function and puts the animal at risk for potentially devastating adverse drug effects. The purpose of this study was to evaluate ABCB1-1Δ gene mutation status in species belonging to the Canidae family, including each of the following: maned wolf (Chrysocyon brachyurus), gray wolf (Canis lupus), red wolf (Canis rufus), coyote (Canis latrans), dingo (Canis lupus dingo), New Guinea singing dog (Canis lupus dingo), arctic fox (Vulpes lagopus), and fennec fox (Vulpes zerda). These species were chosen based on an evolutionary study conducted by Belyaev that noted foxes, bred for temperament, tended to have similar behaviors seen in the modern-day dog. Wolves, known predecessors to the modern dog, were also included. In the current study, a buccal swab was performed on each animal and then tested at Washington State University's Veterinary Clinical Pharmacology Lab, where they were tested according to previously published methods validating buccal swab samples and polymerase chain reaction (PCR) -based genetic analysis. Knowledge of Canidae species ABCB1-1Δ gene mutation status allows for safe and effective therapeutic treatment of nondomestic animals, ensuring any anticipated adverse drug events are prevented. All eight species were found to have the wild-type ABCB1 gene and thus, expected to have normally functioning P-gp efflux transporters. Although these data can be used to guide clinical decision making, because of a small sample size, a more robust study is necessary to assess Canidae ABCB1-1Δ mutation status comprehensively.

Characterization of Veterinary Pharmacy and Pharmacology Literature and its Availability to Pharmacy Education.

Objective. To characterize the veterinary pharmacy and pharmacology literature cited by veterinary drug monographs and journal articles and describe the database indexing and availability of this literature in libraries serving pharmacy schools. Methods. Citations in American Academy of Veterinary Pharmacology and Therapeutics monographs, Journal of Veterinary Pharmacology and Therapeutics (JVPT) articles, and Plumb's Veterinary Drug Handbook, Eighth Edition (Plumb's) were analyzed for publication type and age. Three zones of cited journals were determined by Bradford's Law of Scattering based on citation counts. Results. Monographs most often cited journal articles (1886 [64.7%]), unpublished "grey" literature (632 [21.7%]), and books (379 [13.0%]), but only a few cited proceedings (16 [0.5%]). In JVPT, articles predominated (9625 [91.9%]). Articles comprised 54.8% (1,959) of Plumb's citations; proceedings, 27.0%; books, 15.7%; and grey literature, 2.5%. The age of cited items varied, with 17.1% of monograph citations less than five years old, compared to 26.3% of cited items in JVPT and 40.5% of cited items in Plumb's being less than five years old. Zone 1 consisted of three veterinary journals for monographs, four veterinary journals for Plumb's, and 16 veterinary and human journals for JVPT. Indexing coverage was above 92% in Web of Science, Scopus, and PubMed for zone 1 and 2 journals. Libraries serving both pharmacy and veterinary education programs subscribe to 95% of zone 1 journals, while libraries serving pharmacy education at institutions without a veterinary program subscribe to an average of 59% of zone 1 journals. Conclusion. Veterinary pharmacy and pharmacology literature relies on journals from human and veterinary practice, veterinary proceedings, and, less often, books and drug manufacturer information. Libraries supporting pharmacy programs could contribute to the education of future pharmacists who will be filling veterinary prescriptions by increasing access to this literature.

Highlighting the role of veterinary pharmacists in zoonotic diseases including COVID-19.

Veterinary pharmacy is an often unknown and therefore, underrepresented career path for pharmacists. Uniquely, pharmacists-even untrained in veterinary medicine-are the only health professionals legally allowed to provide care for human and nonhuman patients. The 2019 coronavirus disease (COVID-19) pandemic is a peculiar situation that, not only highlights veterinary pharmacy as a career path, but stresses the role veterinary pharmacists, trained in both human and veterinary medicine, can play in zoonotic diseases. Specialized training in veterinary medicine allows the pharmacist to serve as a resource for both physicians as well as veterinarians during zoonotic events by helping to ascertain feasibility of therapeutic options given the species. In addition, veterinary pharmacists involved in translational research would be vital for the drug development process as they would be aware of biologic nuances between the species and how they may affect the ultimate therapeutic outcome.

Pharmacovigilance in patients with diabetes: A data-driven analysis identifying specific RAS antagonists with adverse pulmonary safety profiles that have implications for COVID-19 morbidity and mortality.

OBJECTIVES: The current demographic information from China reports that 10%-19% of patients hospitalized with coronavirus disease (COVID-19) were diabetic. Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) are considered first-line agents in patients with diabetes because of their nephroprotective effects, but administration of these drugs leads to upregulation of angiotensin-converting enzyme 2 (ACE2), which is responsible for the viral entry of severe acute respiratory distress syndrome coronavirus 2 (SARS-CoV-2). Data are lacking to determine what pulmonary effects ACEIs or ARBs may have in patients with diabetes, which could be relevant in the management of patients infected with SARS-CoV-2. This study aims to assess the prevalence of pulmonary adverse drug effects (ADEs) in patients with diabetes who were taking ACEI or ARBs to provide guidance as to how these medications could affect outcomes in acute respiratory illnesses such as SARS-CoV-2 infection. METHODS: 1DATA, a unique data platform resulting from collaboration across veterinary and human health care, used an intelligent medicine recommender system (1DrugAssist) developed using several national and international databases to evaluate all ADEs reported to the Food and Drug Administration for patients with diabetes taking ACEIs or ARBs. RESULTS: Mining of this data elucidated the proportion of a cluster of pulmonary ADEs associated with specific medications in these classes, which may aid health care professionals in understanding how these medications could worsen or predispose patients with diabetes to infections affecting the respiratory system, specifically COVID-19. Based on this data mining process, captopril was found to have a statistically significantly higher incidence of pulmonary ADEs compared with other ACEIs (P = 0.005) as well as ARBs (P = 0.012), though other specific drugs also had important pulmonary ADEs associated with their use. CONCLUSION: These analyses suggest that pharmacists and clinicians will need to consider the specific medication's adverse event profile, particularly captopril, on how it may affect infections and other acute disease states that alter pulmonary function, such as COVID-19.

Presence of cerebrospinal fluid antibodies associated with autoimmune encephalitis of humans in dogs with neurologic disease.

BACKGROUND: Presumed autoimmune diseases affecting the central nervous system (CNS) of dogs are common. In people, antibodies against neuronal cell surface antigens that are associated with a wide variety of neurological syndromes have been identified. The presence of cerebrospinal fluid (CSF) autoantibodies that target neuronal cell surface proteins has not been reported in dogs with neurologic disorders. OBJECTIVES: Autoantibodies to neuronal cell surface antigens can be found in the CSF of dogs with inflammatory CNS disease. Our aim was to determine whether 6 neuronal cell surface autoantibodies were present in the CSF of dogs diagnosed with inflammatory and noninflammatory CNS disease. ANIMALS: Client-owned dogs with CNS disease and complete diagnostic evaluation including magnetic resonance imaging and CSF analysis were included. One healthy dog was included as a negative control. METHODS: Cerebrospinal fluid was tested for 6 antigenic targets with a commercially available indirect immunofluorescence assay test kit. RESULTS: There were 32 dogs with neurological disease, 19 diagnosed with inflammatory disease (encephalitis and meningitis), 10 with noninflammatory disease (neoplasia, intervertebral disk disease, degenerative myelopathy, and epilepsy), 2 with no diagnosis, and 1 with neoplasia and meningoencephalitis. Anti-N-methyl-d-aspartate receptor 1 (NMDAR1) antibodies were detected in 3 dogs (3/32; 9.38%). All 3 dogs responded to treatment of meningoencephalomyelitis of unknown etiology (MUE). CONCLUSIONS AND CLINICAL IMPORTANCE: Further evaluation of the prevalence and clinical relevance of CSF and serum antibodies to neuronal cell surface antigens is warranted. Defining antigenic targets associated with encephalitis in dogs might allow diagnostic categorization of MUE antemortem.

The pharmacokinetics of gabapentin in cats.

BACKGROUND: Gabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats. Despite this common and chronic usage, clinically relevant pharmacokinetic data is lacking. OBJECTIVES: To evaluate the pharmacokinetics of clinically relevant dosing regimens of gabapentin in cats. ANIMALS: Eight research-purpose mixed-breed cats. METHODS: Cats were enrolled in a serial order, non-randomized pharmacokinetic study. Gabapentin was administered as an IV bolus (5 mg/kg), orally (10 mg/kg) as a single dose or twice daily for 2 weeks, or as a transdermal gel (10 mg/kg) in serial order. Serial blood samples were collected up to 48 hours. Plasma concentrations were determined using Ultra Performance Liquid Chromatography-Mass Spectrometry. Compartmental analysis was used to generate gabapentin time-concentration models. RESULTS: After IV administration CL (median (range)) and terminal half-life were 160.67 mL/kg*hr (119.63-199.11) and 3.78 hours (3.12-4.47), respectively. The oral terminal half-life was 3.63 hours (2.96-4.77), and 3.72 hours (3.12-4.51) for single and repeated dosing. TMAX and CMAX , as predicted by the model were 1.05 hours (0.74-2.11), and 12.42 µg/mL (8.31-18.35) after single oral dosing, and 0.77 hours (0.58-1.64), and 14.78 µg/mL (9.70-18.41) after repeated oral dosing. Bioavailability after a single oral dose was 94.77% (82.46-122.83). IMPORTANCE: Repeated oral dosing of gabapentin did not alter the drug's pharmacokinetics, making dose adjustments unnecessary with long-term treatment. As prepared, the transdermal route is an inappropriate choice for drug administration. These relevant data are important for future studies evaluating potential efficacy of the medication for treating chronic pain states in cats.