Pharmacokinetics and Safety of Sulfamethoxazole-Trimethoprim After Oral Administration of Single and Multiple Doses to Rhode Island Red Chickens (Gallus gallus domesticus).

Sulfamethoxazole-trimethoprim (SMZ-TMP), a commonly prescribed antibiotic for backyard hens, is neither Food and Drug Administration approved nor prohibited in laying hens in the United States. The aim of this study was to determine whether plasma concentrations above targeted minimum inhibitory concentration breakpoint values for Enterobacteriaceae could be achieved with oral dosing. Five Rhode Island red hens (Gallus gallus domesticus) were administered a single dose of 96 mg/kg SMZ-TMP (80 mg/kg SMZ and 16 mg/kg TMP) IV followed by the same dose orally after a washout period. Following oral dosing, mean SMZ concentrations exceeded the target breakpoint for approximately 12 hours; however, TMP only briefly exceeded the target breakpoint. Bioavailability was 60.5% for SMZ and 82.0% for TMP. Ten naïve birds were allocated into control (n = 4) and treatment (n = 6) groups for a 7-day multi-dose study. Treatment birds received an oral suspension dosed at 16 mg/kg TMP and 80 mg/kg SMZ every 48 hours (on days 1, 3, 5, and 7); TMP tablets were additionally dosed at 25 mg/bird on days 1, 3, 5, and 7, and 50 mg/bird on days 2, 4, and 6. Plasma SMZ-TMP concentrations were measured on a multiple time interval by ultraperformance liquid chromatography-mass spectrometry, and pharmacokinetic analyses were performed using a noncompartmental model. No accumulation for either drug was noted following repeated dosing, and no statistical differences in biochemical values, packed cell volumes, or weight were found between pre- and posttreatment in either the treatment or control groups. Sulfamethoxazole (80 mg/kg q48h PO) and TMP (24.1-28.0 mg/kg q24h PO) maintained therapeutic plasma concentrations at or exceeding the minimum inhibitory concentration breakpoint of Enterobacteriaceae for 72 and 24 hours for TMP and SMZ, respectively, without evidence of adverse effects or drug accumulation. Further studies are needed to refine this dosage regimen and evaluate adverse effects in ill birds.

Effects of Intramuscular Alfaxalone and Midazolam Compared With Midazolam and Butorphanol in Rhode Island Red Hens (Gallus gallus domesticus).

Chickens (Gallus gallus domesticus) often undergo veterinary procedures requiring sedation; however, there is little published research evaluating the efficacy of sedation protocols in this species. The objective of this study was to assess the effects of intramuscular alfaxalone and midazolam compared with intramuscular butorphanol and midazolam in chickens. In a complete crossover study, 11 healthy adult hens were randomly administered midazolam 2.5 mg/kg IM combined with either alfaxalone 15 mg/kg IM (AM, n = 11) or butorphanol 3 mg/kg IM (BM, n = 11), with a 35-day washout period between groups. Time to first effects, recumbency, standing, and recovery were recorded. Physiologic parameters and sedation scores were recorded every 5 minutes by 2 blinded investigators. Fifteen minutes after injection, positioning for sham whole body radiographs was attempted. At 30 minutes, flumazenil 0.05 mg/kg IM was administered to all hens. Peak total sedation score was significantly higher for AM compared with BM (P < 0.001). Mean ± SD or median (range) time to initial effects, recumbency, standing, and recovery in AM and BM were 1.9 ± 0.6 and 2.6 ± 0.9 (P = 0.02), 3.5 (1.6-7.6) and 4.8 (2.2-13.0) (P = 0.10), 40.3 (28.0-77.8) and 33.2 (5.2-41.3) (P = 0.15), and 71.2 (45.7-202.3) and 39.9 (35.9-45.9) minutes (P = 0.05), respectively. Radiographic positioning was successful in 6 of 11 (54.5%) and 0 of 11 (0%) birds in the AM and BM groups at 15 minutes, respectively. Heart and respiratory rates remained within acceptable clinical limits for all birds. Intramuscular AM resulted in significantly faster onset of sedative effects, significantly longer duration of recumbency, significantly higher peak sedation, and improved success of radiographic positioning compared with intramuscular BM. Intramuscular AM produces clinically effective sedation in chickens without clinically significant cardiorespiratory effects.

Clinicopathologic, Gross Necropsy, and Histopathologic Effects of High-Dose, Repeated Meloxicam Administration in Rhode Island Red Chickens (Gallus gallus domesticus).

Meloxicam is a commonly prescribed non-steroidal anti-inflammatory drug for backyard poultry that has demonstrated pharmacodynamic efficacy at a single high dose of 5 mg/ kg. This study characterized the adverse effects of meloxicam administered in chickens at an approximate dose of 5 mg/kg orally twice daily for 5 days. Twenty-one adult Rhode Island Red hens (Gallus gallus domesticus), judged to be healthy based on an external physical examination, complete blood count (CBC), and plasma biochemistry panel, were recruited for this study. The subject birds were randomly assigned to a treatment (n = 11) or control group (n = 10) and received a 15-mg tablet of meloxicam or a nonmedicated feed pellet, respectively, orally twice daily. Physical examinations and body weight measurements were performed daily, and observation for clinical signs occurred twice daily. Following completion of the 5-day treatment course, an external physical examination, blood collection for a CBC and plasma biochemistry panel, euthanasia, necropsy, and measurement of meloxicam tissue residues were performed. During the treatment course, 1 hen from the treatment group died with peracute clinical signs, 2 hens from the treatment group died suddenly with no clinical signs, and 1 hen from the treatment group became acutely lethargic and was euthanized. Within the meloxicam group, 7 out of 11 hens had gross and histologic evidence of varying levels of renal acute tubular injury and gout. Plasma uric acid concentrations were above the species reference intervals in all affected hens in the treatment group that were still available for testing. The control group had no evidence of renal injury or gout based on postmortem examinations. Based on the results of this study, repeated oral dosing of meloxicam in chickens at 5 mg/kg twice daily is not recommended.

Evaluation of a nutritional supplement for the alleviation of pain associated with feline degenerative joint disease: a prospective, randomized, stratified, double-blind, placebo-controlled clinical trial.

OBJECTIVES: The purpose of this study was to evaluate the pain-alleviating and activity-enhancing effects of glucosamine/chondroitin sulfate (Dasuquin) in cats that had degenerative joint disease (DJD) and owner-noted mobility/activity impairment. We hypothesized that the nutritional supplement would produce pain-relieving and activity-enhancing effects in cats with painful DJD. METHODS: In this prospective, randomized, stratified, double-blind, placebo-controlled clinical trial, 59 cats with DJD pain were assigned to receive a placebo (n = 30) or supplement (n = 29) for 6 weeks after 2 weeks of placebo. Outcome measures (at-home accelerometry and client-specific outcome measures [feline (CSOMf); Feline Musculoskeletal Pain Index (FMPI); quality of life (QoL)]; and veterinarian examination) were collected at days 14, 28, 42 and 56. RESULTS: Twenty-seven cats in the treatment group and 30 in the placebo group completed the trial. Within the first 2 weeks (placebo administration to all cats), 78% of all cats had an improvement in CSOMf scores. Both groups showed significant improvement at most time points in CSOMf, FMPI, QoL and pain scores, with the placebo group showing greater improvement than the supplement group (significant for CSOMf [P = 0.01]). Overall, no differences in activity were seen between the groups. Cumulative distribution function analysis indicated that for most levels of activity, the placebo-treated cats were more active; however, the least active cats were more active on the supplement (P = 0.013). CONCLUSIONS AND RELEVANCE: This study showed a strong placebo effect. The glucosamine/chondroitin sulfate supplement did not show pain-relieving effects when compared with placebo.

Use of oral trazodone for sedation in cats: a pilot study.

OBJECTIVES: Resistance to transportation and stressful veterinary visits are major causes for a decrease in feline veterinary care. Few options exist for oral sedatives to reduce cats' anxiety prior to veterinary visits. The purpose of this study was to evaluate the safety and efficacy of oral trazodone for use as a single dose agent for sedation in cats. METHODS: Six laboratory cats were given single 50, 75 and 100 mg doses of trazodone and placebo. Trazodone 100 mg and placebo treatments were randomized. Pre- and post-study laboratory values and physical examinations were compared. During each 4 h period post-treatment, sedation was measured via accelerometers and video observations scored by an observer blinded to treatment. Examinations were performed on the cats 90 mins after treatment, and their behavioral responses scored by the same blinded observer. RESULTS: No adverse effects or changes in physical examinations or laboratory values were detected as a result of trazodone administration. Accelerometer data showed trazodone 50, 75 and 100 mg caused sedation as measured by activity reduction (83%, 46% and 66%, respectively). In contrast, there was a 14% activity increase after placebo. There was a significant reduction in video observation scores when cats were given trazodone 100 mg compared with placebo. Mean latency to peak sedation for trazodone 100 mg occurred at 2 h. Scores for behavioral response to examination, performed at 90 mins post-treatment, were not significantly different between cats receiving trazodone 100 mg and placebo. CONCLUSIONS AND RELEVANCE: Trazodone was well tolerated in this population of cats and caused appreciable sedation at all doses. Behavior during examination was not significantly different when cats received trazodone 100 mg compared with placebo. Further studies are recommended to investigate the use of oral trazodone in cats for the purpose of decreasing anxiety assocaited with transportation and examination.

Clinical trials involving cats: what factors affect owner participation?

STUDY RATIONALE: Clinical trials are frequently hindered by difficulties in recruiting eligible participants, increasing the timeline and limiting generalizability of results. In veterinary medicine, where proxy enrollment is required, no studies have detailed what factors influence owner participation in clinical trials involving cats. We aimed to investigate these factors through a survey of owners at first opinion practices. PROTOCOL: The survey was designed using feedback from a pilot study and input from clinical researchers. Owners were asked demographic questions and whether they would, would not, or were unsure about participating in a clinical trial with their cat. They then ranked the importance and influence of various factors on participation using a five-point Likert-type scale, and incentives from most to least encouraging. A total of 413 surveys were distributed to cat owners at four hospitals, two feline-only and two multi-species; 88.6% were completed. Data for importance and influence factors as well as incentive rankings were analyzed overall, and by hospital type, location and whether owners would consider participating. FINDINGS: The most influential factors were trust in the organization, benefit to the cat and veterinarian recommendation. Importance and influence factors varied by willingness to participate. Ranked incentives were not significantly different across groups, with 'Free Services' ranked highest. RELEVANCE: This study provides a first look at what factors influence participation in clinical trials with cats. Given the importance placed in the recommendation of veterinarians, continued work is needed to determine veterinarian-related factors affecting clinical trial participation. The results provide guidance towards improved clinical trial design, promotion and education.

Owner-assessed indices of quality of life in cats and the relationship to the presence of degenerative joint disease.

This study evaluated the types of items owners consider important to their cats' quality of life (QoL). We hypothesized that items contributing to QoL in cats are predominantly items requiring mobility. The objectives of the study were to describe the types of items considered important by owners for their cats' QoL; to describe the proportion of these items that involve mobility; to evaluate what patient factors, including severity of degenerative joint disease (DJD), affect this distribution; and to evaluate whether the proportion of QoL items involving mobility chosen by owners is different in cats presenting for a DJD study compared with a randomly selected population. A total of 830 client-generated items were evaluated. Regardless of DJD status, 40% of items listed by owners involved mobility, while 60% were 'inactive' items, rejecting our hypothesis. This highlights the need to assess non-active items that owners consider to constitute QoL to fully assess the impact of diseases like DJD and, therefore, the success of therapeutic interventions.

Evaluation of a digitally integrated accelerometer-based activity monitor for the measurement of activity in cats.

OBJECTIVE: To assess the correlation between data generated by an accelerometer-based activity monitor and the distance moved in cats. STUDY DESIGN: Prospective experimental study. ANIMALS: Three, four-year-old, male, purpose-bred research cats, weighing between 5.1 and 5.9 kg. METHODS: Part I: Collar and harness mounted accelerometers were evaluated in three cats, comparing simultaneously collected accelerometer data with movement data from computer-analyzed video. Part II: Cats wore collar and harness mounted accelerometers, and data were recorded for 4 weeks to evaluate day-to-day and week-to-week variation in activity. RESULTS: Part I: 432 hours of simultaneous video and accelerometer data were collected. The correlation between accelerometer counts and distance moved was 0.82 overall. Agreement between collar and harness mounted accelerometers was excellent with only 6% of the differences in measurements lying outside the mean difference +/- 2 standard deviations. The adjusted R(2) for harness accelerometer output and 6% mobility was 0.75; for movement 0.84; and for mean velocity 0.83. Evaluation of video indicated eating, grooming and scratching created high accelerometer counts with little effect on movement. Part II: There was a significant effect of day on harness (p < 0.001) and collar (p < 0.002) counts, with counts being lowest at the weekend. There was a significant effect of week on harness-mounted accelerometer counts (p < 0.034), but not on collar-mounted accelerometer counts. Harness accelerometer counts were lowest in week 1. CONCLUSION: Output from an acceleration-based digitally integrated accelerometer correlated well with distance moved and mobility in freely moving cats provided the mobility threshold in the analysis software was > or = 6%. CLINICAL RELEVANCE: Acceleration-based activity monitors may allow for objective measurement of improved mobility following analgesic treatment for conditions such as osteoarthritis.