Non-linear relationship between bioavailability and dose after oral administration of four single doses of acepromazine in dogs and cats

Acepromazine maleate is used in veterinary medicine as a pre-anaesthetic agent. The pharmacokinetics of this drug administered orally in dogs and cats are poorly documented. In an open, single dose, randomised cross-over study, the disposition of acepromazine and the dose-concentration time relationships were studied following single oral administration of 1.25, 2.5, 5 and 10 mgkg bwt, respectively, in 5 dogs and 5 cats. Treatments were allocated randomly to the animals at 10 day intervals. Using high performance liquid chromatography, ACP was determined in blood samples at 0, 5, 20, 40, 60, 90, 120 and 240 min and 8, 12, 18 and 24 h in dogs; and at 0, 30 min and then the same intervals in cats. ACP was detected in 4 of the 5 dogs and in all 5 cats at a dose of 1.25 mgkg bwt. However, in cats, estimation of the apparent elimination half-life at the lowest dose was imprecise due to some very low detectable concentrations during the elimination phase. In dogs, the area under the curve (AUC) increased with the dose but not simply as a linear relationship as indicated by significantly different normalised AUC (AUCD) among the doses. In cats, the concentration curve was higher than in dogs at the same dose per kg bwt. Dose-normalised AUC did not differ significantly between the 4 doses. The apparent elimination half-life remained similar over the tested dose range in both species and was about 2.5 h in dogs and 3 h in cats. The relationship between oral absorption of acepromazine and the dose (range 1.25 to 10 mgkg bwt) was consistent with pre-systemic metabolism becoming saturated at the higher dose (10 mgkg bwt) in dogs and at a lower dose in cats (between 2.5 and 5 mgkg bwt) or with a saturable absorption.     

The potential of the combined use of targeted type I interferon pathway inhibitors and oncolytic viruses to treat sarcomas

Replicating oncolytic viruses (OVs) are appealing, new, FDA‐approved, therapeutic options for humans with head and neck cancers and melanomas. These treatments are not yet available for veterinary patients, but recent clinical trials have shown several OVs to be safe in dogs and cats. Specific viruses being used to treat sarcomas in dogs include modified canine adenovirus 2, myxoma virus, vesicular stomatitis virus and reovirus. In cats with vaccine‐associated sarcomas, poxviruses have been injected postoperatively and a reduced rate of tumour recurrence was documented. To date, the response rates of canine and feline patients to OV therapy have been variable (as they are in people). Optimal methods of OV administration and dosing schedules continue to be evaluated. One way to improve outcomes of OV therapy in veterinary patients may be to use OVs in combination with other immunomodulatory therapies. This review discusses the potential utility of concurrent therapy with an OV and an inhibitor of the type I interferon pathway.     

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs

Opioids used in the pre‐operative period may frequently induce vomiting. Acepromazine is commonly combined with opioids as a pre‐anesthetic drug, and has antiemetic properties. The purpose of this study was to evaluate the antiemetic properties of acepromazine in dogs receiving opioids as a pre‐anesthetic. One hundred and sixteen dogs (ASA I or II), 58 males and 58 females; purebreds and mixed breeds; 3 months?13.4 years of age; weighing 1.8–57.7 kg admitted for elective surgical procedures, were randomly assigned to one of the three groups. All groups received acepromazine (0.05 mg kg^?1 IM). Group I (n = 40) received acepromazine 15 minutes prior to opioid administration. Group II (n = 38) received acepromazine in combination with the opioid. Group III (n = 38) received acepromazine 15 minutes after opioid administration. One of the three different opioids was administered IM to each dog: morphine at 0.5 mg kg^?1, hydromorphone at 0.1 mg kg^?1, or oxymorphone at 0.075 mg kg^?1. Statistical analysis included a χ²‐test for the incidence of vomiting and a Kruskal–Wallis nonparametric test for the sedation comparison between groups. The dogs receiving acepromazine before the opioid (Group I) had significantly lower incidence of vomiting (18%) than those in Groups II (45%) and III (55%). The degree of sedation assessed 15 minutes after administration of the last drug (s) in each group was significantly lower in the dogs receiving the combination of acepromazine and opioid (Group II) than in those receiving opioid as the first drug (Group III). Time to vomiting was less than 8 minutes in all groups. In conclusion, acepromazine administered 15 minutes before opioid reduces the incidence of vomiting induced by opioids.     

Recombinant human thyrotropin in veterinary medicine: current use and future perspectives

Recombinant human thyrotropin (rhTSH) was developed after bovine thyrotropin (bTSH) was no longer commercially available. It was approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) as an aid to diagnostic follow-up of differentiated thyroid carcinoma in humans and for thyroid remnant ablation with radioiodine. In addition, rhTSH is used in human medicine to evaluate thyroid reserve capacity and to enhance radioiodine uptake in patients with metastatic thyroid cancer and multinodular goiter. Likewise, rhTSH has been used in veterinary medicine over the last decade. The most important veterinary use of rhTSH is thyroidal functional reserve testing for the diagnosis of canine hypothyroidism. Recent pilot studies performed at Ghent University in Belgium have investigated the use of rhTSH to optimize radioiodine treatment of canine thyroid carcinoma and feline hyperthyroidism. Radioiodine treatment optimization may allow a decreased therapeutic dosage of radioiodine and thus may improve radioprotection. This review outlines the current uses of rhTSH in human and veterinary medicine, emphasizing research performed in dogs and cats, as well as potential future applications.     

One Health in Practice: A Pilot Project for Integrated Care of Zoonotic Infections in Immunocompromised Children and Their Pets in Chile

Although pets provide physiological and psychological benefits to their owners, they are a potential source of zoonotic infections, especially for vulnerable individuals such as immunocompromised patients. During 1 year, we therefore performed a pilot project, which included 32 immunocompromised Chilean children and their family pets (35 dogs and 9 cats) with the aim of detecting, treating and preventing zoonotic infections. Children were examined by Infectious Diseases paediatricians and demographical and clinical information related to zoonotic infections were recorded. Pets were examined and sampled by veterinarians, who also administered missing routine vaccines and anti‐parasitics. During family visits, all members were informed and educated about zoonoses and a satisfaction survey was performed. Visits also included vector control and indoor residual spraying with pyrethroids. Children were re‐examined and re‐tested according to the findings of their pets, and all detected zoonotic infections were treated both in children and pets. Physical examination revealed abnormalities in 18 dogs (51.4%) and three cats (33.3%). Twenty‐eight (63.6%) of the pets were diagnosed with a zoonotic pathogen, and seven (15.9%) with a facultative pathogen. Most zoonotic agents were isolated from the pet's external ear and intestine. Bacteria with the highest pathogenic potential were Campylobacter jejuni and Brucella canis. In two children and their respective pets, the same zoonotic diseases were diagnosed (toxocariasis and giardiasis). Arthropods serving as potential vectors of zoonotic infections were found in 49% of dogs and 44% of cats. The pilot project was positively evaluated by the participating families. Our pilot project confirmed that pets are reservoir for various zoonotic agents in Chile and that the implementation of an integrated multidisciplinary programme was a valuable tool to prevent, diagnose and treat such zoonotic infections in vulnerable patients such as immunocompromised children.     

Gastroprotectants in small animal veterinary practice – a review of the evidence. Part 1: cyto‐protective drugs

Diverse drugs with presumed cytoprotective effect have been used therapeutically in small animal veterinary practice for various gastro‐intestinal conditions such as oesophagitis, gastric ulceration, gastritis or chronic gastro‐enteropathies. Their efficacy has been doubted in human medicine, raising similar questions in the veterinary field. The aim of this review was to assess the current evidence on the efficacy and safety of these drugs in dogs and cats. Through a systematic review of the literature, we identified 37 articles on the use of misoprostol, sucralfate and other gastroprotectants in dogs and cats. There was evidence to support use of misoprostol in the prevention of aspirin‐induced gastroduodenal mucosal injury in dogs, and for use of sucralfate in the prevention of acid‐induced oesophagitis in cats. However, the overall quality of evidence supporting the use of these drugs in small animal patients was poor. In contrast, there was evidence of important adverse effects, especially drug interaction and gastro‐intestinal signs. We therefore recommend prescribing these drugs with caution until further well‐conducted studies reveal a useful gastroprotectant effect.     

Prevalence of interfering antibodies in dogs and cats evaluated using a species‐independent assay

Background

Interfering antibodies in human serum and plasma are known to react with mammalian antibodies in immunoassays and cause false‐positive test results. Although this phenomenon was recently shown in companion animals, knowledge regarding immunoassay interference in veterinary medicine is very limited.

Objectives

The aims of this study were to set up a species‐independent immunoassay procedure to detect interference in serum samples, to screen for interference in a cross‐section of canine and feline patient samples from an animal hospital, and to determine if the detected interference could be neutralized using an immunoassay based on nonmammalian reagents.

Methods

A 2‐site sandwich‐type interference assay was set up using commercially available mouse reagents. A total of 369 serum samples from 320 dogs and 263 samples from 218 cats were analyzed using the interference assay. Multiple samples were submitted from 36 dogs and 39 cats. Nineteen samples identified as interference‐positive were analyzed in an assay using chicken antibodies.

Results

Interference was detected in samples from 28 dogs (9%) and 10 cats (5%) screened with the interference assay. Except for 1 cat, consistent results were obtained for all 75 dogs and cats that submitted more than 1 sample. The interference was eliminated when analyzed in the chicken‐based assay (P < .001).

Conclusions

Substances with reactivity toward mouse IgG can be detected in serum samples from dog and cat patients using a 2‐site interference assay. The detected substances are most likely interfering antibodies, possibly originating from immunization with other mammalian species.     

Effects of acepromazine on the incidence of vomiting associated with opioid administration in dogs

Objective To evaluate the anti‐emetic properties of acepromazine in dogs receiving opioids as pre‐anesthetic medication. Study design Randomized prospective clinical study. Animals One hundred and sixteen dogs (ASA I or II), admitted for elective surgical procedures. The dogs were a mixed population of males and females, purebreds and mixed breeds, 0.25–13.4 years of age, weighing 1.8–57.7 kg. Methods A prospective clinical trial in which the dogs were randomly assigned to one of three groups. All groups received acepromazine (0.05 mg kg^?1 intramuscularly (IM)). Group I received acepromazine 15 minutes prior to opioid administration. Group II received acepromazine in combination with the opioid. Group III received acepromazine 15 minutes after opioid administration. One of three different opioids was administered IM to each dog: morphine sulfate at 0.5 mg kg^?1; hydromorphone hydrochloride at 0.1 mg kg^?1; or oxymorphone hydrochloride at 0.075 mg kg^?1. Results Dogs receiving acepromazine before the opioid (group I) had a significantly lower incidence of vomiting (18%) than dogs in groups II (45%) and III (55%). The degree of sedation was significantly lower in the dogs receiving the combination of acepromazine and the opioid (group II) than in dogs receiving the opioid as the first drug (group III). Conclusions and clinical relevance Acepromazine administered 15 minutes before the opioid lowers the incidence of vomiting induced by opioids.     

Cephalosporins – pharmacological basis of clinical use in veterinary dermatology

Cephalosporins form a large group of β-lactam antibiotics which are used extensively in human medicine and to a lesser extent in domestic animals. In veterinary dermatology, the principle use for the cephalosporins is the clinical management of canine pyoderma associated with Staphylococcus intermedius . In practice, the use of orally administered first generation cephalosporin drugs to affected dogs is well tolerated and highly efficacious. Bacterial drug resistance appears to occur rarely.     

Molecular characterization of community‐associated methicillin‐resistant Staphylococcus aureus from pet dogs

Community‐associated methicillin‐resistant Staphylococcus aureus (MRSA) is a serious public health concern and in Australia, one that disproportionately affects Aboriginal people. Paralleling MRSA in human medicine, methicillin‐resistant S. pseudintermedius (MRSP) is an increasingly prevalent pathogen in veterinary medicine. We aimed to characterize the carriage of MRSA and MRSP in dogs and cats from predominantly Aboriginal communities in a very remote region of New South Wales (NSW), Australia. Pets (303 dogs and 80 cats) were recruited from six communities in western NSW. Three swabs were collected from each animal (anterior nares, oropharynx and perineum) and from skin lesions or wounds (if present) and cultured on selective media for methicillin‐resistant staphylococci. Human host‐adapted community‐associated MRSA representing four multilocus sequence types (ST1‐IV, ST5‐IV, ST72‐IV, ST93‐IV) were isolated from eight dogs (prevalence 2.6%, 95% confidence interval 1.3%–5.1%). Two ST5‐IV isolates from a single dog were phenotypically trimethoprim‐resistant, harbouring trimethoprim‐resistant gene dfrG within the SCCmec type IVo mobile genetic element. MRSA was not isolated from any cats and MRSP was not isolated from any dogs or cats. This study estimated a high prevalence of human host‐adapted community‐associated MRSA carriage in dogs despite an absence of MRSP. This suggests MRSA carried by dogs in remote NSW originate from human hosts. The cycle of transmission between people, dogs and common environmental sources warrants further investigation. To our knowledge, this is the first report of trimethoprim‐resistant ST5‐IV in eastern Australia and the first report of trimethoprim‐resistant ST5‐IV from a dog.     

A review of anaemia of inflammatory disease in dogs and cats

Anaemia of inflammatory disease is a common cause of anaemia in routine veterinary practice. It is most often mild to moderate, normocytic, normochromic and non‐regenerative. Shortened red cell life span, inhibition of iron metabolism and impaired bone marrow response to erythropoietin all contribute to its development. Although anaemia of inflammatory disease is a well‐known cause of anaemia in dogs and cats, there is a lack of epidemiological information because specific diagnostic criteria have not been established in veterinary species. Anaemia of inflammatory disease is associated with a poor outcome in various disease states in human medicine; however, its clinical significance and treatment in veterinary medicine are not well understood. This review article describes anaemia of inflammatory disease in dogs and cats and considers its potential significance.     

Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2010

In 2010, we observed again an increase in the number of declarations reported to the vigilance system for veterinary medicinal products up to a total of 160. The species and drug classes reported remained the same as in previous years: the majority of adverse drug reactions (ADRs) concerned either dogs or cats and the most frequently involved drugs were either antiparasitic products or antiinfectives. Adverse reactions following reconversions and 8 cases of suspected allergic reactions following the use of amoxicillin-clavulanic acid combinations in dogs were reported. Additional enquiries were processed by the Swiss Toxicological Information Centre and transmitted to Swiss medic. 11 of these reported accidental ingestions of flavoured tablets in overdose by dogs and some cats. The vaccino vigilance program received 179 declarations following immunization against blue tongue disease as well as 82 declarations following the application of other vaccines. The vigilance system increases the chance to identify rare reactions or interactions and thereby contributes to the security of veterinary medicinal products.     

Validation of the Sysmex XT‐2000iV hematology system for dogs,cats, and horses. I. Erythrocytes,platelets, and total leukocyte counts

Background: The Sysmex XT‐2000iV is a laser‐based, flow cytometric hematology system that has been introduced for use in large and referral veterinary laboratories. Objective: The purpose of this study was to validate the Sysmex XT‐2000iV for counting erythrocytes, reticulocytes, platelets, and total leukocytes in blood from ill dogs, cats, and horses. Methods: Blood samples from diseased animals (133 dogs, 65 cats, and 73 horses) were analyzed with the Sysmex XT‐2000iV and the CELL‐DYN 3500. Manual reticulocyte counts were done on an additional 98 canine and 14 feline samples and manual platelet counts were done on an additional 73 feline and 55 canine samples, and compared with automated Sysmex results. Results: Hemoglobin concentration, RBC counts, and total WBC counts on the Sysmex were highly correlated with those from the CELL‐DYN (r≥0.98). Systematic differences occurred for MCV and HCT. MCHC was poorly correlated in all species (r=0.33–0.67). The Sysmex impedance platelet count in dogs was highly correlated with both the impedance count from the CELL‐DYN (r=0.99) and the optical platelet count from the Sysmex (r=0.98). The Sysmex optical platelet count included large platelets, such that in samples from cats, the results agreed better with manual platelet counts than with impedance platelet counts on the Sysmex. Canine reticulocyte counts on the Sysmex correlated well (r=0.90) with manual reticulocyte counts. Feline reticulocyte counts on the Sysmex correlated well with aggregate (r=0.86) but not punctate (r=0.50) reticulocyte counts. Conclusion: The Sysmex XT‐2000iV performed as well as the CELL‐DYN on blood samples from dogs, cats, and horses with a variety of hematologic abnormalities. In addition, the Sysmex detected large platelets and provided accurate reticulocyte counts.     

Incomplete surgery,local immunostimulation,and recurrence of some tumour types in dogs and cats

Summary

Histologically confirmed inadequate treatment resulted in a lower than expected recurrence percentage in dogs with haemangiopericytoma (38%) and mastocytoma (30%). Clinical suspicion of inadequate tumour treatment did not always correlate with the histologically assessed inadequacy, nor with the appearance of local recurrence. Local recurrence did not seem to be correlated with histological grade of malignancy and tumour size. Local injection of C. parvum vaccine did not result in a lower percentage of local recurrence or longer recurrence free intervals in any of the three tumour groups (canine haemangiopericytoma, canine mastocytoma, feline mammary carcinoma). Nor was palliative local adjuvant injection of Cp successful in dogs and cats with soft tissue sarcomas or in dogs with gingival melanoma. Re‐operation of locally recurrent tumour was successful in some dogs with haemangiopericytoma, in a few with mastocytoma, but not in cats with mammary carcinoma. A trend toward histological progression of recurrences and metastases, when compared with the primary tumours, was not evident. The possible reasons for the relatively low recurrence rate of some tumour types and for the failure of Cp‐treatment are discussed.     

Clinical and in vitro efficacy of amoxicillin against bacteria associated with feline skin wounds and abscesses

A clinical trial involving 122 cats with infected skin wounds or abscesses presented to 10 veterinary clinics was conducted to evaluate the efficacy of 2 oral amoxicillin drug products (a paste and a suspension). A 2nd objective of the study was to identify bacteria involved in such infections and verify their in vitro sensitivity to amoxicillin. Samples of wound exudate were harvested at the time of presentation and submitted for aerobic and anaerobic culture. The sensitivity to amoxicillin of isolates thought to be infecting agents was tested, using a standard minimum inhibitory concentration method. Pasteuralla multocida and obligate anaerobes of the genera Prevotella, Fusobacterium, and Porphyromonas were the most frequently isolated pathogens. Overall, their in vitro susceptibility to amoxicillin was very good. Both drug products were clinically efficacious with a global success rate of 95.1% for cats administered oral amoxicillin at 11-22 mg/kg bodyweight (mean 13.8 mg/kg bodyweight) twice daily for 7 to 10 days.     

The use of ciclosporin A in veterinary dermatology

Ciclosporin A (CsA) has potent immunosuppressive and immunomodulatory activity that has been exploited in human medicine to prevent the rejection of transplanted organs and to manage atopic dermatitis and psoriasis. Over the past decade, CsA has been employed more frequently in veterinary dermatology and its value in the management of several canine and feline dermatoses is now well established. CsA inhibits calcineurin phosphatase, suppressing T cell activation and the synthesis of T cell cytokines consequently impairing the activity of B cells, antigen-presenting cells, mast cells, basophils and eosinophils. The pharmacokinetics of CsA are similar in humans, dogs and cats and the drug has a wide safety margin in dogs, cats and rabbits. Adverse effects, principally transient vomiting and soft faeces/diarrhoea, may be seen shortly after instituting treatment but often resolve despite continuing treatment. Gingival hyperplasia and cutaneous effects such as hirsutism may occur after prolonged treatment.     

Establishment of a cell line for assessing drugs as canine P‐glycoprotein substrates: proof of principle

P‐glycoprotein (P‐gp), encoded by the ABCB1 (MDR1) gene, dramatically impacts drug disposition. P‐gp is expressed in the intestines, biliary canaliculi, renal tubules, and brain capillaries where it functions to efflux substrate drugs. In this capacity, P‐gp restricts oral absorption, enhances biliary and renal excretion, and inhibits central nervous system entry of substrate drugs. Many drugs commonly used in veterinary medicine are known substrates for canine P‐gp (vincristine, loperamide, ivermectin, others). Because these drugs have a narrow therapeutic index, defective P‐gp function can cause serious adverse drug reactions due to enhanced brain penetration and/or decreased clearance. P‐gp dysfunction in dogs can be intrinsic (dogs harboring ABCB1‐1Δ) or acquired (drug interactions between a P‐gp inhibitor and P‐gp substrate). New human drug candidates are required to undergo assessment for P‐gp interactions according to FDA and EMA regulations to avoid adverse drug reactions and drug–drug interactions. Similar information regarding canine P‐gp could prevent adverse drug reactions in dogs. Because differences in P‐gp substrates have been documented between species, one should not presume that human or murine P‐gp substrates are necessarily canine P‐gp substrates. Thus, our goal was to develop a cell line for assessing drugs as canine P‐gp substrates.     

PHYSIOLOGIC VARIANTS,BENIGN PROCESSES,AND ARTIFACTS FROM 106 CANINE AND FELINE FDG‐PET/COMPUTED TOMOGRAPHY SCANS

18F‐Fluoro‐deoxyglucose positron emission computed tomography (FDG‐PET/CT) is an emerging diagnostic imaging modality in veterinary medicine; however, little published information is available on physiologic variants, benign processes, and artifacts. The purpose of this retrospective study was to describe the number of occurrences of non‐neoplastic disease‐related FDG‐PET/CT lesions in a group of dogs and cats. Archived FDG‐PET/CT scans were retrieved and interpreted based on a consensus opinion of two board‐certified veterinary radiologists. Non‐neoplastic disease‐related lesions were categorized as physiologic variant, benign activity, or equipment/technology related artifact. If the exact cause of hypermetabolic areas could not be determined, lesions were put into an indeterminate category. A total of 106 canine and feline FDG‐PET/CT scans were included in the study. In 104 of the 106 scans, a total of 718 occurrences of physiologic variant, areas of incidental benign activity, and artifacts were identified. Twenty‐two of 23 feline scans and 82 of 83 canine scans had at least one artifact. Previously unreported areas of increased radiopharmaceutical uptake included foci associated with the canine gall bladder, linear uptake along the canine mandible, and focal uptake in the gastrointestinal tract. Benign activity was often seen and related to healing, inflammation, and indwelling implants. Artifacts were most often related to injection or misregistration. Further experience in recognizing the common veterinary FDG physiologic variation, incidental radiopharmaceutical uptake, and artifacts is important to avoid misinterpretation and false‐positive diagnoses.     

雾化吸入疗法在宠物疾病临床中的应用

雾化吸入疗法是当今兽医临床较为理想的一种给药途径。介绍了该疗法在治疗犬、猫等宠物疾病中的适应症及其药物的选择,以及在应用时注意的事项,从而使雾化吸入疗法能够在犬、猫等宠物临床疾病治疗中发挥更好的作用。     

Vigilance for veterinary medicinal products: declarations of adverse reactions in the year 2009

During the year 2009, 134 reports of suspected adverse drug reactions (ADRs) to veterinary medicinal products (VMPs) were received (106 in the year 2008). The distribution according to species and drug classes remained in line with previous years. Companion animals were involved in most of the reports (46 % dogs, 19 % cats), followed by cattle or calves (22 %). Antiparasitic drugs made the biggest part with 30 % of the reports, followed by antiinfectives (19 %) and hormones (13 %). Some reactions following their use are specifically discussed. 95 additional enquiries about ADRs of VMPs were received by the Swiss Toxicological Information Centre in Zürich. Most of them concerned dogs or cats and antiparasitics or anti-inflammatory drugs. In the vaccinovigilance program, a total of 1020 reports were received, of which 1000 were related to the vaccination against blue tongue disease. The most frequently reported adverse reactions were aborts, mastitis or alterations of milk quality and they are specifically discussed.