Two-Way Crossover Phase 1 Bioequivalence and Safety Studies in Healthy Adults for a Ready-to-Use, Room-Temperature, Liquid-Stable Glucagon Administered by Autoinjector, Prefilled Syringe, or Vial and Syringe.

OBJECTIVE: To demonstrate bioequivalence and safety for a ready-to-use room-temperature liquid-stable glucagon administered subcutaneously (SC) through a glucagon autoinjector (GAI) or a glucagon vial and syringe kit (GVS), versus a glucagon prefilled syringe (G-PFS). METHODS: Healthy adults (N = 32) were randomly assigned to receive 1-mg glucagon as GAI or G-PFS, and then as the alternative three to seven days later. Other healthy adults (N = 40) were randomly assigned to receive 1-mg glucagon as GVS or G-PFS, and then as the alternative two days later. Samples for plasma glucagon were obtained through 240 minutes after glucagon injection. Bioequivalence was declared when the geometric mean estimate ratio of the area under-the-concentration-versus-time curve from 0 to 240 minutes (AUC0-240) and maximum concentration (Cmax) for plasma glucagon between treatment groups was contained within the bounds of 80% and 125%. Adverse events (AEs) were recorded. RESULTS: The 90% confidence intervals (CIs) for AUC0-240 and Cmax geometric mean ratios for G-PFS to GAI and GVS to G-PFS were contained within the bounds 80% to 125% (G-PFS:GAI AUC0-240 95.05%, 119.67% and Cmax 88.01%, 120.24%; GVS:G-PFS AUC0-240 87.39%, 100.66% and Cmax 89.08%, 106.08%). At least one AE occurred in 15.6% (5/32) participants with GAI, 25% (18/72) with G-PFS, and 32.5% (13/40) with GVS. Sixty-nine of 73 (94.5%) AEs were mild, and none were serious. Nausea was the most common (33/73 [45%]). CONCLUSIONS: Bioequivalence and safety were established after 1 mg of this ready-to-use room-temperature liquid-stable glucagon, administered SC to healthy adults, by autoinjector, prefilled syringe, or vial and syringe kit.

Antibodies produced by dogs successfully challenged with live Leptospira spp. did not cross-react to Brucella antigen in a commercial rapid slide agglutination test that detects antibodies to Brucella canis.

Brucella canis is a cause of canine infertility and abortion. Veterinarians and veterinary laboratorians screen for antibodies to B. canis with serologic tests including a rapid slide agglutination test (RSAT; D-Tec CB, Zoetis, San Diego, CA). False-positive results are possible because of cross-reactivity to antibodies to some gram-negative bacteria. Cross-reactivity has been reported between antibodies of Brucella abortus and Leptospira spp. with serologic tests for bovine brucellosis; however, this has not been documented with serologic tests for canine brucellosis, to the author's knowledge. The RSAT was evaluated with the sera from dogs experimentally challenged with 1 of 4 serovars of Leptospira spp.: L. kirschneri serovar Grippotyphosa, or L. interrogans serovars Canicola, Icterohaemorrhagiae, or Pomona. Experimental infections were confirmed through results of microscopic agglutination testing and/or lateral flow immunochromatography testing. The sera of 32 dogs collected at day 0 and days 7, 10, and 14 yielded negative results with the RSAT. Antibodies produced through experimental infections to these 4 serovars of Leptospira spp. did not cross-react with Brucella antigen with the RSAT; therefore, cross-reactivity of anti-leptospiral antibodies may not be of concern for B. canis rapid slide agglutination testing of dogs.

Evaluation of a Community's Risk for Canine Parvovirus and Distemper Using Antibody Testing and GIS Mapping of Animal Shelter Intakes.

This cross-sectional study aimed to identify where dogs with negative antibody tests to canine parvovirus (CPV) and canine distemper virus (CDV) originated when entering a community shelter, using a commercially available ELISA antibody test and Geographic Information Systems mapping. Of 2745 canines entering during a three-month period, 1056 test results were obtained. Dogs or puppies weighing over 2 lb were eligible if they could be humanely, nonchemically restrained for phlebotomy. Age and minor health issues weren't exclusions. Dogs were excluded if trained personnel were concerned health would be compromised by phlebotomy. Blood samples were collected within 24 hours of entry. Four hundred and twenty-seven (40%) dogs had positive antibody test results for both viruses, 422 (40%) were positive for CPV, 37 (4%) were positive for CDV, and 170 (16%) were negative for both. Mapping revealed geographic patterns for dogs with negative antibody tests. This shelter admitted dogs with negative CPV and/or CDV antibody tests from defined community areas. Targeting vaccination efforts in communities to areas where dogs with negative antibody tests originate could be an effective wellness strategy.

Diagnostic performances of two rapid tests for detection of feline leukemia virus antigen in sera of experimentally feline leukemia virus-infected cats.

OBJECTIVES: The objective of this study was to compare the diagnostic sensitivities and specificities of WITNESS FeLV-FIV (Zoetis) and SNAP FIV/FeLV Combo Test (IDEXX) for the detection of FeLV p27 antigen in the sera of experimentally feline leukemia virus (FeLV)-infected cats. METHODS: Diagnostic sensitivities of WITNESS and SNAP were determined through testing of 47 serum samples collected from cats day 56 post-experimental infection with a virulent FeLV Rickard strain. Successful experimental infection was confirmed based on observation of FeLV antigen and proviral DNA in anti-coagulated (EDTA) whole-blood samples by immunofluorescent antibody (IFA) test and PCR, respectively. Diagnostic specificities of both tests were determined through testing of sera of 92 laboratory-housed, non-FeLV-exposed specific pathogen-free (SPF) cats. RESULTS: Forty-one of 47 blood samples were IFA positive, whereas all 47 samples were PCR positive. All 92 non-FeLV-infected SPF cats were IFA and PCR negative. In comparison to IFA as the reference method, both WITNESS and SNAP tests yielded equivalent sensitivities and specificities of 100% and 97.8%, respectively. In comparison to PCR as the reference method, both WITNESS and SNAP tests likewise performed equivalently, with sensitivities and specificities of 91.5% and 100%, respectively. CONCLUSIONS AND RELEVANCE: Sensitivity and specificity of WITNESS FeLV-FIV for identifying FeLV p27 antigen in the sera of these experimentally FeLV-infected and non-FeLV-exposed SPF cats equaled those of the SNAP FIV/FeLV Combo Test. However, all positive results, regardless of the point-of-care test used, should be confirmed before making clinical decisions such as segregation from other cats or euthanasia.

Accuracy of a point-of-care luteinizing hormone test for help in distinguishing between sexually intact and ovariectomized or castrated domestic cats.

Objectives The aim of this study was to determine the accuracy of a commercial luteinizing hormone (LH) test as an aid in distinguishing between sexually intact and ovariectomized or castrated domestic cats. Methods Convenience serum samples collected from sexually intact female and male cats (n = 67) undergoing elective sterilization surgery and archived sera from ovariectomized and castrated cats (n = 54) were tested for LH using a commercial diagnostic assay. Test results were compared with the known reproductive status of the cats. Additionally, sera from sexually intact (n = 54) and ovariectomized (n = 94) queens were collected at specific times of the year to evaluate possible seasonal effects on test results. Results Overall test sensitivity was 89.3% (95% confidence interval [CI] 82.3-94.2%), specificity was 92.6% (95% CI 87.1-96.2%) and accuracy was 91.1%. Analysis of results of female cats (n = 216) - sexually intact (n = 87) and ovariectomized (n = 129) - yielded a test sensitivity of 90.8% (95% CI 82.7-96.0%), a specificity of 92.3% (95% CI 86.2-96.2%) and accuracy of 91.7%. Analysis of the results of male cats (n = 53) - sexually intact (n = 19) and neutered (n = 34) - yielded test a sensitivity of 85.3% (95% CI 68.9-95.1%), a specificity of 94.7% (95% CI 74.0-99.9%) and accuracy of 88.7%. The sera of 10 intact queens unexpectedly yielded positive LH results; two of these cats were in estrus, based on visual inspection at the time of ovariohysterectomy. Test accuracy was 94.6% for those 148 samples collected at specific times of the year, with two samples each over three, 3 month periods yielding false-positive results. Conclusions and relevance The commercial point-of-care LH test is a useful adjunct to historical and physical examination findings for determination of reproductive status in domestic cats. Repeat testing 24 h later should be considered for those female cats with signs of estrus and initial positive test results.

Kinetics and postmucosal effects on urinary recovery of 5 intravenously administered sugars in healthy cats.

The objective of this study was to describe the kinetics of urinary recovery and to evaluate the effects of postmucosal factors on urinary recovery of 5 intravenously administered saccharides. Ten cats received an isotonic sugar solution containing lactulose, rhamnose, xylose, methylglucose, and sucrose intravenously. These sugars were selected because of their prior use for intestinal permeability and mucosal function testing in humans and dogs. Urethral catheterization with a closed collection system was used for collection of cumulative urine samples prior to and 2, 4, 6, 8, 10, 12, and 24 h after administration of the sugar solution. High-pressure anion exchange liquid chromatography with pulsed amperometric detection was used to measure the concentrations of each sugar in the urine and calculate urinary recovery. Twenty-four hour cumulative urinary recovery for each sugar from the cats, was lower than expected compared to dogs and humans. All 5 sugars had the highest percentage of urinary recovery during the first 2 h after administration. Mean sugar elimination rate constants and half-lives ranged from 0.268/h for methylglucose to 0.415/h for lactulose and 1.67 h for lactulose to 2.59 h for methylglucose, respectively. Metabolism and incomplete urine collection are possible reasons for lower cumulative urinary recoveries of these 5 sugars in cats compared with dogs. Although these 5 sugars are not ideal marker molecules, they may still be useful for intestinal permeability and mucosal function testing in cats.