Effects of deracoxib and aspirin on serum concentrations of thyroxine, 3,5,3'-triiodothyronine, free thyroxine, and thyroid-stimulating hormone in healthy dogs

OBJECTIVE: To evaluate the effects of deracoxib and aspirin on serum concentrations of thyroxine (T4), 3,5,3'-triiodothyronine (T3), free thyroxine (fT4), and thyroid-stimulating hormone (TSH) in healthy dogs. ANIMALS: 24 dogs. PROCEDURE: Dogs were allocated to 1 of 3 groups of 8 dogs each. Dogs received the vehicle used for deracoxib tablets (PO, q 8 h; placebo), aspirin (23 to 25 mg/kg, PO, q 8 h), or deracoxib (1.25 to 1.8 mg/kg, PO, q 24 h) and placebo (PO, q 8 h) for 28 days. Measurement of serum concentrations of T4, T3, fT4, and TSH were performed 7 days before treatment (day -7), on days 14 and 28 of treatment, and 14 days after treatment was discontinued. Plasma total protein, albumin, and globulin concentrations were measured on days -7 and 28. RESULTS: Mean serum T4, fT4, and T3 concentrations decreased significantly from baseline on days 14 and 28 of treatment in dogs receiving aspirin, compared with those receiving placebo. Mean plasma total protein, albumin, and globulin concentrations on day 28 decreased significantly in dogs receiving aspirin, compared with those receiving placebo. Fourteen days after administration of aspirin was stopped, differences in hormone concentrations were no longer significant. Differences in serum TSH or the free fraction of T4 were not detected at any time. No significant difference in any of the analytes was detected at any time in dogs treated with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: Aspirin had substantial suppressive effects on thyroid hormone concentrations in dogs. Treatment with high dosages of aspirin, but not deracoxib, should be discontinued prior to evaluation of thyroid function.     

The effect of dosing interval on the efficacy of misoprostol in the prevention of aspirin-induced gastric injury

The effect of twice-daily administration of misoprostol on aspirin-induced gastric injury was evaluated. Twenty-four random-source dogs were divided into groups that received aspirin and misoprostol as follows: group I, aspirin 25 mg/kg PO q8h and placebo PO q8h; group II, aspirin 25 mg/kg PO q8h and misoprostol 3 microg/kg PO q8h; group III, aspirin 25 mg/kg PO q8h, misoprostol 3 microg/kg PO q12h, and placebo PO q24h; and group IV, aspirin 25 mg/kg PO q8h, misoprostol 3 microg/kg PO q24h, and placebo PO q12h for 28 days. Gastroscopy was performed on days -9, 5, 14, and 28. Visible lesions were scored on a scale of 1 (mucosal hemorrhage) to 11 (perforating ulcer). No difference in total score was identified between groups I and IV on any day. Median total scores for groups II and III were significantly (P < or = .05) lower compared to groups I and IV on day 5. Group III had a significantly lower score (P < or = .05) than groups I, II, and IV on day 28. This study suggests that misoprostol 3 microg/kg PO q12h is as effective as misoprostol 3 microg/kg PO q8h in preventing aspirin-induced gastric injury in this model. However, misoprostol 3 microg/ kg PO q8h was less effective in preventing aspirin-induced gastric injury on days 14 and 28 than in previous studies. No difference among numbers of dog-days of vomiting, diarrhea, or anorexia was detected among groups.     

Cyclooxygenase expression and prostanoid production in pyloric and duodenal mucosae in dogs after administration of nonsteroidal anti-inflammatory drugs

OBJECTIVE: To assess cyclooxygenase (COX) expression and prostanoid concentrations in pyloric and duodenal mucosae of dogs after administration of nonsteroidal anti-inflammatory drugs (NSAIDs). ANIMALS: 8 healthy dogs. PROCEDURES: Each dog received carprofen (4.4 mg/kg, q 24 h), deracoxib (2 mg/kg, q 24 h), aspirin (10 mg/kg, q 12 h), and placebo (1 dog treat, q 24 h) orally for 3 days (4-week interval between treatments). Before study commencement (baseline) and on day 3 of each treatment, pyloric and duodenal mucosal appearance was assessed endoscopically and biopsy specimens were obtained for histologic examination. Cyclooxygenase-1 and COX-2 protein expressions were assessed via western blotting, and prostanoid concentrations were measured via ELISAs. An ANOVA was used to analyze data. RESULTS: Treatments had no effect on mucosal appearance and ulceration was not evident histologically. In pyloric and duodenal mucosae, COX-1 expression was unaffected by treatments. Cyclooxygenase-2 expression remained unchanged in pyloric mucosa; in duodenal mucosa, aspirin significantly increased COX-2 expression, compared with effects of deracoxib and carprofen. At baseline, total prostaglandin and thromboxane B2 concentrations in pyloric mucosa were significantly greater than those in duodenal mucosa. Aspirin significantly decreased both prostanoid concentrations in both mucosal tissues, compared with other treatments. In pyloric mucosa, carprofen administration significantly decreased total prostaglandin and thromboxane B2 concentrations, compared with deracoxib administration. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs, prostanoid synthesis was greater in pyloric mucosa than it was in duodenal mucosa. Nonselective NSAIDs significantly decreased prostanoid concentrations in these mucosae, compared with the effects of a selective COX-2 NSAID.     

Effects of Prednisone Alone or Prednisone with Ultralow-Dose Aspirin on the Gastroduodenal Mucosa of Healthy Dogs

Background: The coadministration of prednisone and ultralow-dose aspirin has been recommended for the management of various diseases, but the safety of this combination in dogs has not been studied.
Hypotheses: The gastroduodenal lesions associated with prednisone and ultralow-dose aspirin administration will be similar to those caused by prednisone alone, but both treatments will result in more severe lesions than placebo.
Animals: Eighteen healthy adult purpose-bred dogs.
Methods: Randomized, blinded, placebo-controlled study of 3 treatment groups for 27 days: placebo, prednisone, and prednisone and aspirin. Gastroduodenoscopy was performed before and on days 5, 14, and 27 of treatment and mucosal lesions scores were assigned. Mucosal lesion scores were compared by a Kruskal-Wallis test. Clinical signs were compared by the Friedman's chi-square test (significance at P < .05).
Results: There were no significant differences in the gastroduodenal lesion scores among groups, or within groups at any time during the study. Significantly more dog-days of diarrhea occurred in the prednisone and aspirin group during treatment, compared with baseline. No significant differences in clinical signs were found among any of the groups.
Conclusion: The concurrent use of prednisone and ultralow-dose aspirin did not increase the severity of gastroduodenal lesions compared with prednisone or placebo. Coadministration of prednisone and ultralow-dose aspirin increases the frequency of mild, self-limiting diarrhea in some dogs.     

Changes in platelet function, hemostasis, and prostaglandin expression after treatment with nonsteroidal anti-inflammatory drugs with various cyclooxygenase selectivities in dogs

OBJECTIVE: To determine the effects of nonsteroidal anti-inflammatory drugs of various cyclooxygenase selectivities on hemostasis and prostaglandin expression in dogs. ANIMALS: 8 client-owned dogs with clinical signs of osteoarthritis. PROCEDURES: Dogs received aspirin (5 mg/kg, PO, q 12 h), carprofen (4 mg/kg, PO, q 24 h), deracoxib (2 mg/kg, PO, q 24 h), and meloxicam (0.1 mg/kg, PO, q 24 h) for 10 days each, with an interval of at least 14 days between treatments. On days 0 and 10, blood was collected for platelet aggregation assays, thrombelastography, and measurement of lipopolysaccharide-stimulated prostaglandin E(2), platelet thromboxane B(2) (TXB(2)), and free serum TXB(2) and 6-keto-prostaglandin F (PGF)-1alpha concentrations. RESULTS: Platelet aggregation decreased after treatment with aspirin and carprofen, whereas significant changes from baseline were not detected for the other drugs tested. Thrombelastograms obtained after treatment with carprofen revealed decreased maximum amplitude and alpha-angle, suggesting hypocoagulability. Maximum amplitude and coagulation index increased after treatment with deracoxib. Plasma concentrations of prostaglandin E(2) decreased after treatment with carprofen or deracoxib, and platelet TXB(2) production increased after treatment with aspirin. Serum concentrations of the prostacyclin metabolite 6-keto-PGF-1alpha did not change significantly after treatment with any of the drugs, although the ratio of free TXB(2) to 6-keto-PGF-1alpha decreased slightly after treatment with carprofen and increased slightly after treatment with deracoxib. CONCLUSIONS AND CLINICAL RELEVANCE: At the dosages tested, treatment with meloxicam affected platelet function minimally in dogs with osteoarthritis. Treatment with carprofen decreased clot strength and platelet aggregation. Clot strength was increased after treatment with deracoxib.     

The Gastroduodenal Effects of Buffered Aspirin, Carprofen, and Etodolac in Healthy Dogs

Twenty-four healthy mixed-breed dogs were divided into 4 groups. Group 1 received a placebo p.o. q12h, group 2 received an average of 16.5 (15.1-17.8) mg/kg buffered aspirin p.o. q12h, group 3 received an average of 2.2 (2.0-2.4) mg/kg carprofen p.o. q12h, and group 4 received an average of 12.8 (11.7-13.8) mg/kg etodolac p.o. q24h (with a placebo in the PM). All treatments continued for 28 consecutive days. Gastroduodenal endoscopy was performed on days -9, 0, 5, 14, and 28. Multiple gastric biopsies were obtained endoscopically on day -9 to determine each dog's Helicobacter infection status. Four regions in the stomach and 1 region in the proximal duodenum were evaluated endoscopically, and each was assigned a score from 1 to 11. Scores for each region then were summed to give a total score for each endoscopic evaluation. Erosions and submucosal hemorrhages were seen in all dogs receiving aspirin. Only minor gastric lesions were observed in the carprofen, etodolac, and control groups. No adverse clinical signs were noted in any dog given any treatment. Median total score on days 0, 5, 14, and 28, respectively, were as follows: group 1: 5.0, 5.0, 5.0, 5.0; group 2: 5.0, 27.0, 26.0, 27.5; group 3: 5.0, 5.0, 6.0, 5.0, group 4: 5.0, 7.0, 5.0, 5.0. There was no significant difference among dogs receiving carprofen, etodolac, or placebo. The administration of carprofen, etodolac, or placebo to healthy dogs resulted in significantly less gastroduodenal lesion development than in dogs receiving buffered aspirin.     

Colloid oncotic pressure and total protein changes in horses during anesthesia fluid therapy

It is unknown whether overlapping or sequential use of nonsteroidal anti‐inflammatory (NSAIDs) results in an increased risk for gastrointestinal (GI) ulceration. The purpose of this pilot study was to evaluate the GI effects of various combinations of an injectable NSAID followed by an oral NSAID, a scenario often employed clinically for management of the pre‐ and post‐operative canine patient. Six healthy Walker hounds received four treatment regimens in a randomized, cross‐over design with a 2 week washout period between each treatment week: carprofen (4 mg kg^–1, SQ) followed by placebo (PO, q24 × 4 days); placebo (SQ) followed by deracoxib (3–4 mg kg^–1, PO, q24 × 4 days); carprofen (4 mg kg^–1, SQ) followed by carprofen (4 mg kg^–1, PO, q24 × 4 days); carprofen (4 mg kg^–1, SQ) followed by deracoxib (3–4 mg kg^–1, PO, q24 ×4 days). Weekly bloodwork (CBC, biochemistry panel, fecal evaluation, fecal occult blood) and daily clinical scoring (TPR, vomiting, diarrhea, appetite) were obtained. GI endoscopy was performed on days –2, 1, 2, 5, and 11 days post treatment of each treatment period and lesions scored using a previously reported 6‐point scale. Data was analyzed using a mixed anova for repeated measures. There were no significant differences in clinical or clinicopathologic data between groups. Within the carprofen‐carprofen and carprofen‐deracoxib groups, lesions worsened by Day 5 (1 day after last oral dose) for the fundic and antral regions (p < 0.05). Fundic, antral and lesser curvature lesions improved by Day 5 in the carprofen‐placebo group and lesser curvature lesions improved in the placebo‐deracoxib group (p < 0.05). No significant within‐group differences were noted for the esophagus, cardia or duodenum. The small number of dogs precludes general conclusions about the safety of sequential NSAID use, but these results suggest that a larger scale study is warranted.     

The effects of epidural deracoxib on the ground reaction forces in an acute stifle synovitis model

OBJECTIVE: To evaluate the efficacy of epidurally administered deracoxib to mediate the signs of a sodium urate crystal-induced stifle synovitis in dogs, and to compare the efficacy of epidural versus subcutaneously administered deracoxib. STUDY DESIGN: Experimental, randomized, blinded, placebo-controlled modified cross-over design. ANIMALS: Random source, adult, mixed breed dogs (n = 24; 14 males, 10 females). METHODS: Sodium urate crystals were used to create a stifle synovitis model to evaluate the efficacy of deracoxib. Dogs were divided into 4 groups: 3 mg/kg epidural deracoxib, 1.5 mg/kg epidural deracoxib, 3 mg/kg subcutaneous deracoxib, and a placebo (vehicle for deracoxib). Force plate and subjective evaluations were made at time 0, 2, 4, 8, 12, and 24 hours post-treatment. Repeated measures ANOVA with Bonferroni-corrected post hoc comparisons was used to determine significant treatment effects. RESULTS: Peak vertical force (PVF) and vertical impulse (VI) were both significantly higher in deracoxib treated dogs compared with placebo. For 3 mg/kg epidural and subcutaneous deracoxib, PVF and VI were significantly greater than for 1.5 mg/kg epidural deracoxib. Overall pain score for all deracoxib-treated dogs was significantly lower than for placebo dogs. CONCLUSIONS: Epidural administration of deracoxib is effective at providing analgesia in an acute joint pain model; however, it does not appear to be more effective than systemic administration. CLINICAL RELEVANCE: Injectable deracoxib is effective in providing analgesia in acute inflammatory conditions of synovial joints.     

The Effect of Misoprostol on Aspirin-Induced Gastroduodenal Lesions in Dogs

Misoprostol, a synthetic prostaglandin E₁, analog, is effective in treating and preventing nonsteroidal antiin-flammatory drug (NSAID)-induced gastrointestinal lesions in humans. The effectiveness of misoprostol in preventing aspirin-induced gastroduodenal injury was studied in 3 groups of 6 adult mixed breed dogs. Group I received 3 μg/kg misoprostol PO tid. Group II received 3 μg/kg misoprostol PO tid and 35 mg/kg aspirin PO tid. Group III received 35 mg/kg aspirin PO tid. Endoscopy was performed on days 0, 5, 14, and 30. Five regions of the upper gastrointestinal tract were qualitatively scored from 1 to 12 based on the presence of submucosal hemorrhage, erosion, or ulceration, with ulceration receiving a higher numerical score than submucosal hemorrhage. A total score was assigned based on the sum of the scores from all regions. Comparisons among groups on each day were performed using the Kruskal-Wallis test. Differences within a group among different time periods were determined using appropriate multiple comparisons. Significant difference in mean gastroduodenal lesion score was found among all groups at 5, 14, and 30 days. Mean total score on days 5, 14, and 30 were as follows: group 1,5.0,5.2, 9.0; group II, 12.0, 12.7, 16.2; and group III, 26.0, 23.8, 21.5, respectively. Significant differences within a group among different time periods were found from days 0 to 5 in groups I and II, and from days 14 to 30 in group I. It was concluded that misoprostol effectively decreased endoscopically detectable mucosal lesions in dogs given aspirin.     

Effect of short-term sequential administration of nonsteroidal anti-inflammatory drugs on the stomach and proximal portion of the duodenum in healthy dogs

OBJECTIVE: To evaluate effects of injection with a nonsteroidal anti-inflammatory drug (NSAID) followed by oral administration of an NSAID on the gastrointestinal tract (GIT) of healthy dogs. ANIMALS: 6 healthy Walker Hounds. PROCEDURES: In a randomized, crossover design, dogs were administered 4 treatments consisting of an SC injection of an NSAID or control solution (day 0), followed by oral administration of an NSAID or inert substance for 4 days (days 1 through 4). Treatment regimens included carprofen (4 mg/kg) followed by inert substance; saline (0.9% NaCl) solution followed by deracoxib (4 mg/kg); carprofen (4 mg/kg) followed by carprofen (4 mg/kg); and carprofen (4 mg/kg) followed by deracoxib (4 mg/kg). Hematologic, serum biochemical, and fecal evaluations were conducted weekly, and clinical scores were obtained daily. Endoscopy of the GIT was performed before and on days 1, 2, and 5 for each treatment. Lesions were scored by use of a 6-point scale. RESULTS: No significant differences existed for clinical data, clinicopathologic data, or lesion scores in the esophagus, cardia, or duodenum. For the gastric fundus, antrum, and lesser curvature, an effect of time was observed for all treatments, with lesions worsening from before to day 2 of treatments but improving by day 5. CONCLUSIONS AND CLINICAL RELEVANCE: Sequential administration of NSAIDs in this experiment did not result in clinically important gastroduodenal ulcers. A larger study to investigate the effect of sequential administration of NSAIDs for longer durations and in dogs with signs of acute and chronic pain is essential to substantiate these findings.     

Efficacy of maropitant in the prevention of delayed vomiting associated with administration of doxorubicin to dogs

Background: Vomiting, nausea, inappetence, and diarrhea are common delayed adverse effects of doxorubicin. Maropitant, a neurokinin‐1 receptor antagonist, is known to prevent acute vomiting in dogs receiving cisplatin. Objective: To evaluate the efficacy of maropitant in preventing delayed vomiting after administration of doxorubicin to dogs. Animals: Fifty‐nine dogs with cancer. Methods: This randomized, double‐blind, placebo‐controlled study used a cross‐over design. Dogs were randomized into 1 of 2 treatment groups. Group A received maropitant after the 1st doxorubicin, and placebo after the 2nd. Group B received placebo first, and maropitant second. Maropitant (2 mg/kg) or placebo tablets were administered PO for 5 days after doxorubicin treatment. Owners completed visual analog scales based on Veterinary Cooperative Oncology Group‐Common Terminology Criteria for Adverse Events to grade their pet's clinical signs during the week after administration of doxorubicin. Statistical differences in gastrointestinal toxicosis and myelosuppression between maropitant and placebo treatments were evaluated. Results: Significantly fewer dogs had vomiting (P= .001) or diarrhea (P= .041), and the severity of vomiting (P < .001) and diarrhea (P= .024) was less the week after doxorubicin when receiving maropitant compared with placebo. No differences were found between maropitant and placebo for other gastrointestinal and bone marrow toxicoses. Conclusions and Clinical Importance: Maropitant is effective in preventing delayed vomiting induced by doxorubicin. Its prophylactic use might improve quality of life and decrease the need for dose reductions in certain dogs.     

Effect of tylosin on dogs with suspected tylosin-responsive diarrhea: a placebo-controlled,randomized, double-blinded,prospective clinical trial

Background

The macrolid antibiotic tylosin has been widely used to treat canine chronic diarrhea, although its efficacy is based on anecdotal reports and experimental studies in dogs and not on strong scientific evidence. The term tylosin-responsive diarrhea (TRD) refers to diarrheal disorders responding to tylosin therapy within a few days. In TRD, the stool remains normal as long as tylosin treatment continues, but diarrhea reappears in many dogs within weeks after discontinuation. The aim of our trial was to assess the effect of tylosin on fecal consistency compared with a placebo treatment in dogs with suspected TRD and additionally to establish whether tylosin in dogs with recurrent diarrhea is as effective as empirical studies and anecdotal reports suggest.

Methods

Subjects comprised 71 client-owned dogs that, according to the owners, had previously been treated successfully with tylosin due to recurrent diarrhea of unknown etiology. At the initial examination, where there were no signs of diarrhea, the dogs were randomly assigned in a 2:1 ratio to a tylosin or placebo group. During a two-month follow-up the owners evaluated the fecal consistency according to previously published guidelines. When diarrhea recurred, either tylosin (25 mg/kg q 24 h, 7 days) or placebo treatment was initiated orally. Treatment outcome was evaluated as the mean of fecal consistency scores assigned during the last three days of the treatment period. To test for differences between the tylosin and placebo group in the proportion of responders, Pearson''s Chi-squared test and Fisher''s exact test were applied.

Results

Sixty-one dogs met the selection criteria and were followed for two months. During the follow-up 27 dogs developed diarrhea and either tylosin or placebo treatment was started. The proportion of dogs with normal fecal consistency at the end of treatment was 85% (17/20) in the tylosin group and 29% (2/7) in the placebo group (Pearson''s Chi-squared test p = 0.0049 and Fisher''s exact test two-sided, p = 0.0114).

Conclusions

Our findings indicate that tylosin is effective in treating recurrent diarrhea in dogs. The dose of 25 mg/kg once daily appears sufficient. No changes specific to TRD were detected in the examinations.     

Multicenter randomized prospective clinical evaluation of meloxicam administered via transmucosal oral spray in client‐owned dogs

The clinical safety and efficacy of a transmucosal oral spray (TMOS) formulation of meloxicam was evaluated for the control of pain and inflammation associated with osteoarthritis in dogs. A total of 280 client‐owned dogs were enrolled at fourteen veterinary clinics: there were 187 dogs in the meloxicam TMOS group and 93 in the placebo control group. Dogs received placebo or treatment spray once daily for twenty‐eight days. Improvement in signs of osteoarthritis was measured using client‐specific outcome measures (CSOM) made at days 14 and 28 and veterinary assessments of lameness and pain on palpation made at day 28. A significantly higher number of dogs in the meloxicam TMOS group were treatment successes at 28 days (72.6%) compared with the placebo group (46.9%), based on CSOM scores. Total CSOM scores were significantly lower in the meloxicam TMOS‐treated group compared with the placebo group at both 14 and 28 days. Differences between treatment groups were not observed in veterinary assessments. Gastrointestinal effects of meloxicam were observed in some animals. Meloxicam TMOS was found to be safe and effective in dogs for the control of pain and inflammation associated with osteoarthritis.     

Gastrointestinal tract perforation in dogs treated with a selective cyclooxygenase-2 inhibitor: 29 cases (2002-2003)

OBJECTIVE: To identify factors associated with gastrointestinal tract perforation in dogs being treated with a selective cyclooxygenase-2 (COX-2) inhibitor (deracoxib). DESIGN: Retrospective study. ANIMALS: 29 dogs. PROCEDURE: The Novartis Animal Health pharmacovigilance database was searched for records of dogs treated with deracoxib in which gastrointestinal tract perforation was documented. Results-16 of the 29 (55%) dogs had received deracoxib at a dosage higher than that approved by the FDA for the particular indication being treated, with 25 (86%) dogs having received deracoxib at a dosage > 2 mg/kg/d (0.9 mg/lb/d). Seventeen (59%) dogs had received at least 1 other nonsteroidal anti-inflammatory drug (NSAID) or a corticosteroid in close temporal association (within 24 hours) with deracoxib administration (ie, immediately before or following). In all, 26 (90%) dogs had received deracoxib at a higher-than-approved dosage or had received at least 1 other NSAID or corticosteroid in close temporal association with deracoxib administration. Twenty dogs died or were euthanatized, and 9 survived. CONCLUSIONS AND CLINICAL RELEVANCE: In dogs with gastrointestinal tract perforation and that had been treated with deracoxib, perforation was most likely attributable to a number of factors. Deracoxib should only be used at approved dosages. Cortico-steroids and other less selective NSAIDs should not be administered in close temporal association with selective COX-2 inhibitors, including deracoxib. Further study is required to define this problem.     

Systematic Review of Nonsteroidal Anti‐Inflammatory Drug‐Induced Adverse Effects in Dogs

The aim of this systematic review was to identify, assess, and critically evaluate the quality of evidence of nonsteroidal anti‐inflammatory drug (NSAID)‐induced adverse effects in dogs. Original prospective studies published in peer‐reviewed journals in English (1990–2012) that reported data on the safety of NSAIDs administration in dogs were searched. For each study, design type (I, II, III, or IV) and assessment of quality (+, Ø, ?) were rated. For each drug, quantity and consistency rating (***, **, *) and strength of evidence (high, moderate, low, or extremely low) were identified and evaluated. The strength of evidence was defined in terms of how applicable and relevant the conclusions were to the target population. Sixty‐four studies met the inclusion criteria. Thirty‐five (55%) research studies and 29 (45%) clinical trials were identified. A high strength of evidence existed for carprofen, firocoxib, and meloxicam; moderate for deracoxib, ketoprofen, and robenacoxib; and low for etodolac. Quality and consistency rating were as follows: carprofen (***/***), deracoxib (**/***), etodolac (*/unable to rate), firocoxib (***/**), ketoprofen (**/***), meloxicam (***/***), and robenacoxib (**/**), respectively. Adverse effects were detected in 35 studies (55%) and commonly included vomiting, diarrhea, and anorexia. Three studies (5%) reported a power analysis related to adverse effects of ≥80%. In randomized, placebo‐controlled, blinded studies (n = 25, 39%), the incidence of adverse effects was not statistically different between treated and control dogs. Finally, most studies were not appropriately designed to determine the safety of NSAIDs, and involved a healthy nongeriatric population of research dogs.     

Robenacoxib vs. carprofen for the treatment of canine osteoarthritis; a randomized, noninferiority clinical trial

Robenacoxib is a member of the coxib class of nonsteroidal anti-inflammatory drugs (NSAID), with high selectivity for the cyclooxygenase (COX)-2 isoform of COX. In this study, the efficacy and tolerability of robenacoxib were compared with those of carprofen in canine osteoarthritis in a multi-centre, prospective, randomized, blinded, positive-controlled noninferiority clinical trial. Both drugs were administered orally once daily at recommended dosages: robenacoxib at 1-2 mg/kg (n = 125 dogs) and racemic carprofen at 2-4 mg/kg (n = 63 dogs) for a total of 12 weeks. The efficacy of the test compounds was assessed by veterinary investigators and owners using numerical rating scales at baseline and days 7, 14, 28, 56 and 84. In both groups, all scores were significantly (P < 0.0001) improved compared with baseline at all time points (days 7-84). Robenacoxib had noninferior efficacy to carprofen for the primary endpoint, the global functional disability, both for all dogs and for the subgroup of dogs in which robenacoxib was not administered during meals. Noninferiority was also demonstrated for three of six veterinary investigator secondary endpoints and four of six owner efficacy endpoints. For haematology and clinical chemistry variables, there were some significant differences from baseline levels but no differences between groups. There were no differences between groups in the frequencies of adverse events, which were reported in 46% dogs with robenacoxib and 52% with carprofen (P = 0.44), which were most frequently mild events affecting the gastrointestinal tract. In conclusion, noninferior efficacy and tolerability of robenacoxib compared with carprofen was demonstrated in dogs with osteoarthritis.     

Comparison of the upper gastrointestinal effects of etodolac and aspirin in healthy dogs.

Fifteen healthy castrated male dogs were separated into three treatment groups that were administered etodolac, aspirin and a placebo orally, respectively. All treatments were continued for 28 days. The animals were examined endoscopically on days 0, 3, 7, 10, 14, 17, 21, 24 and 28. There were no gastrointestinal mucosal lesions in either the etodolac or the placebo group, whereas some gastric lesions developed in the aspirin group after day 17. We considered that etodolac could be used for long-term treatments in dogs with fewer side-effects on the gastric mucosa than aspirin.     

Superiority of the gastroduodenal safety profile of licofelone over rofecoxib, a COX-2 selective inhibitor, in dogs

This study assessed the gastroduodenal safety profile of licofelone, a new nonsteroidal anti-inflammatory drug with dual inhibitory activity against 5-lipoxygenase and cyclo-oxygenase (COX), by using endoscopic evaluations and by comparing licofelone to rofecoxib, a selective COX-2 inhibitor. Twenty-one dogs underwent blinded gastroduodenoscopies, during which the mucosa of the gastroduodenal tract was assessed and scored. Blood analyses were monitored on days 0 (baseline), 14, 28, 42, and 56. Examinations to detect fecal occult blood were performed daily. Dogs were randomly assigned to three groups that received either a placebo, licofelone at a dose of 2.5 mg/kg twice daily, or rofecoxib at a dose of 0.5 mg/kg daily, respectively. Significant differences between the groups in gastric (P = 0.003), duodenal (P = 0.009), and gastroduodenal (P = 0.002) endoscopic lesion scores were observed at day 56. Rofecoxib-treated dogs had more lesions in all areas when compared with placebo-treated dogs, more duodenal lesions when compared with licofelone-treated dogs and more lesions than they had at baseline. In contrast to licofelone, rofecoxib was found to induce significant gastric and gastroduodenal lesions in dogs that lacked pre-existing lesions at baseline. Blood analyses and fecal examinations did not reveal abnormalities in any of the experimental groups. Treatment with licofelone was well tolerated and was shown to be safer than rofecoxib in terms of upper gastrointestinal damage. In this way, this study demonstrates the gastroduodenal safety profile of licofelone for chronic treatment.     

Effects of meloxicam on severity of lameness and other clinical signs of osteoarthritis in dogs

OBJECTIVE: To evaluate effects of meloxicam on severity of lameness and other clinical signs in dogs with osteoarthritis (OA). DESIGN: Randomized, controlled, multicenter clinical trial. ANIMALS: 217 client-owned dogs with clinical and radiographic signs of OA. PROCEDURE: Dogs were randomly assigned to be treated with meloxicam (n = 105; 0.2 mg/kg [0.09 mg/lb], SC, once on day 1, then 0.1 mg/kg [0.045 mg/lb], PO, q 24 h, for 13 days) or a placebo (n = 112). A general clinical score was assigned by investigators on days 1 (ie, prior to initiation of treatment), 8, and 15 on the basis of severity of lameness, extent of weight bearing, and severity of signs during palpation of the affected joint. Owners and investigators provided overall evaluations on days 8 and 15. RESULTS: Dogs treated with meloxicam had significantly greater improvements in general clinical scores, compared with baseline scores, on days 8 and 15 than did dogs treated with placebo. On days 8 and 15, percentages of dogs treated with meloxicam in which owners and investigators considered treatment to be successful were significantly higher than percentages of control dogs in which treatment was considered to be successful. No abnormalities in hematologic and serum biochemical test results were detected. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that compared with administration of a placebo, administration of meloxicam for 14 days significantly improved the clinical condition of dogs with OA without causing adverse effects.     

Efficacy and safety of dirlotapide in the management of obese dogs evaluated in two placebo-controlled, masked clinical studies in North America

Dirlotapide was evaluated in the management of obesity in dogs in two multicenter, clinical studies in North America. A total of 335 obese dogs of various breeds were randomized to dirlotapide or placebo in a 2:1 ratio. Dirlotapide was administered orally once daily to dogs at an initial dose of 0.05 mg/kg, increased after 14 days to 0.1 (study B, label dose) or 0.2 mg/kg (study A) and then adjusted according to individual weight loss at 28-day intervals. Dogs were examined and weighed, and body condition scores (BCSs) were recorded every 28 days. Study A had three consecutive phases: weight loss (16 weeks, day 0–112); weight management (12 weeks); and post-treatment (8 weeks). Study B had a weight loss phase only. For dirlotapide-treated dogs, mean weight loss by day 112 was 11.8–14.0% compared with 3.0–3.9% for placebo ( P  = 0.0001). In study A, weight losses for dirlotapide were 19.3% after 12 weeks of weight management and 16.7% (regain of 3.4%) by 8 weeks after dirlotapide was discontinued. In both studies, dogs in both treatments had emesis, lethargy, anorexia, diarrhea, and mildly elevated hepatic transaminase activity, that resolved spontaneously with time. These were experienced more frequently with dirlotapide. Improved activity levels and BCS for >50% dogs were reported with dirlotapide. Dirlotapide was safe and effective in the reduction and management of body weight in obese dogs.