Long-term efficacy and safety of firocoxib in the treatment of dogs with osteoarthritis

Thirty-nine client-owned dogs with osteoarthritis were treated with 5 mg/kg firocoxib administered orally, once a day for 52 weeks. Veterinary examinations were performed on approximately days 0, 15, 90, 180, 270 and 360. Twenty-five dogs completed the study. The withdrawal rate associated with gastrointestinal side effects was low (5.1 per cent of dogs). Based on the owners' assessment, 82 per cent of the dogs had improved at day 15, 84 per cent of the 32 remaining dogs had improved at day 90, and 96 per cent of the 25 dogs that completed the trial had improved at day 360. During this trial, 12 (48 per cent) of the 25 remaining dogs showed an improvement in their lameness from day 90 to day 360 (P<0.05).     

Comparison of efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis

OBJECTIVE: To compare efficacy and safety of paste formulations of firocoxib and phenylbutazone in horses with naturally occurring osteoarthritis. DESIGN: Randomized controlled clinical trial. ANIMALS: 253 client-owned horses with naturally occurring osteoarthritis. PROCEDURES: Horses were treated with firocoxib (0.1 mg/kg [0.045 mg/lb], PO, q 24 h) or phenylbutazone (4.4 mg/kg [2 mg/lb], PO, q 24 h) for 14 days. Physical examinations and lameness evaluations were performed prior to treatment and after 7 and 14 days. Clinical improvement was defined as a reduction of at least 1 lameness grade or a combined reduction of at least 3 points in scores for pain during manipulation or palpation, joint swelling, joint circumference, and range of motion. RESULTS: Proportion of horses clinically improved on day 14 for the firocoxib group (104/123 [84.6%]) was not significantly different from the proportion for the phenylbutazone group (103/119 [86.6%]). Proportion of horses that were improved on day 14 was significantly greater for horses treated with firocoxib than for horses treated with phenylbutazone with regard to score for pain on manipulation or palpation (P = 0.028), joint circumference score (P = 0.026), and range of motion score (P = 0.012), but not for overall lameness score or joint swelling score. No direct treatment-related adverse effects were detected during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that overall clinical efficacy of a paste formulation of firocoxib in horses with naturally occurring osteoarthritis was comparable to efficacy of a paste formulation of phenylbutazone.     

Efficacy and safety of firocoxib in the management of canine osteoarthritis under field conditions

A total of 249 client-owned dogs with osteoarthritis were treated with firocoxib (5 mg/kg/day) or a positive control, etodolac (10-15 mg/kg/day), for 30 days. Veterinary examinations were performed on approximately days 0 (visit 1), 14 (visit 2), and 29 (visit 3). Based on defined noninferiority criteria, firocoxib and etodolac were comparable. Based on the magnitude of the change from baseline, improvement with firocoxib was significantly greater than with etodolac for lameness at a trot (visits 2 and 3) and for lameness at a walk, pain on manipulation, and range of motion (visit 3) (P < .05). In weekly owner evaluations, firocoxib provided significantly greater improvement than etodolac (P < .05) at each scoring.     

Comparison of the effects of firocoxib, carprofen and vedaprofen in a sodium urate crystal induced synovitis model of arthritis in dogs

A randomized, placebo-controlled, four-period cross-over laboratory study involving eight dogs was conducted to confirm the effective analgesic dose of firocoxib, a selective COX-2 inhibitor, in a synovitis model of arthritis. Firocoxib was compared to vedaprofen and carprofen, and the effect, defined as a change in weight bearing measured via peak ground reaction, was evaluated at treatment dose levels. A lameness score on a five point scale was also assigned to the affected limb. Peak vertical ground reaction force was considered to be the most relevant measurement in this study. The firocoxib treatment group performed significantly better than placebo at the 3 h post-treatment time point and significantly better than placebo and carprofen at the 7 h post-treatment time point. Improvement in lameness score was also significantly better in the dogs treated with firocoxib than placebo and carprofen at both the 3 and 7 h post-treatment time points.     

Effectiveness of the homeopathic preparation Zeel compared with carprofen in dogs with osteoarthritis

The authors compared the symptomatic effectiveness of a complex homeopathic preparation Zeel (1-3 tablets orally per day depending on body weight) to carprofen (4 mg/kg body weight) in dogs (n=68) aged >1 yr diagnosed with osteoarthritis in a multicenter, prospective, observational open-label cohort study in 12 German veterinary clinics. The active treatment period was 56 days. Symptomatic effectiveness, lameness, stiffness of movements, and pain on palpation were evaluated by treating veterinarians and owners. Clinical signs of osteoarthritis improved significantly (P<0.05) at all time points (days 1, 28, and 56) with both therapies. At the end of the treatment period, effectiveness was comparable in both groups. Both treatment regimens were well tolerated with only three treatment-related adverse events, all in the carprofen group.     

Effect of carprofen, etodolac, meloxicam, or butorphanol in dogs with induced acute synovitis

OBJECTIVE: To compare the analgesic and anti-inflammatory effect of single doses of carprofen, etodolac, meloxicam, and butorphanol in dogs with induced acute synovitis (acute pain model) via kinetic gait analysis and orthopedic evaluation and examine measurement of serum C-reactive protein (CRP) concentration as an indicator of treatment efficacy. ANIMALS: 12 Beagles and 6 additional Beagles that were used only in serum CRP analyses. PROCEDURE: Acute synovitis was induced in right stifle joints of dogs via intra-articular injection of monosodium urate solution. Treatments included butorphanol (0.2 mg/kg, i.v.), carprofen (4 mg/kg, PO), etodolac (17 mg/kg, PO), or meloxicam (0.2 mg/kg, PO); control dogs received no treatment. The procedure was repeated (3-week intervals) until all dogs received all treatments including control treatment. Lameness was assessed on a biomechanical force platform and via orthopedic evaluations of the stifle joints; blood was collected to monitor serum CRP concentration. RESULTS: Compared with control dogs, treated dogs had significantly different vertical ground reaction forces and weight-bearing scores. Greatest improvement in lameness was observed in carprofen-treated dogs. Etodolac had the fastest onset of action. Compared with butorphanol treatment, only carprofen and etodolac were associated with significantly lower pain scores. An increase in serum CRP concentration was detected after intra-articular injection in all dogs; this change was similar among groups. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen, etodolac, and meloxicam had greater efficacy than butorphanol in relief of acute pain. Carprofen was most effective overall. In this acute pain model, serum CRP analysis was not useful to assess drug efficacy.     

Efficacy, safety and palatability of a new broad-spectrum anthelmintic formulation in dogs

The efficacy, safety and palatability of a new flavoured chewable anthelmintic tablet were investigated in dogs. The efficacy, based on worm counts, of a single recommended therapeutic dose (RTD) of 5 mg pyrantel + 20 mg oxantel + 5 mg praziquantel/kg bodyweight was assessed in experimental infections (EI) and natural infections (NI) with Trichuris vulpis, Echinococcus granulosus and Toxocara canis. For T vulpis, the efficacy of the treatment was 99.3 per cent in EI (comparing groups of six treated and six control dogs) and 100 per cent in NI (nine treated and nine control dogs). For E granulosus, the efficacy was more than 99.9 per cent in EI (11 treated and 11 control dogs). For T canis, the efficacy was 94.3 per cent in EI (10 treated and 10 control dogs) and 100 per cent in NI (12 treated and 13 control dogs). In a field study, Ancylostoma caninum (11 dogs) and T canis (11 dogs) faecal egg counts were reduced by more than 99 per cent, and in eight dogs with Dipylidium caninum proglotides in the faeces the efficacy was 100 per cent. The tablets were readily consumed by 56 of 64 (87.5 per cent) privately owned dogs. Safety was assessed in groups of six dogs treated either once with twice the RTD, once with six times the RTD, with twice the RTD on three consecutive days, or untreated. There were no significant differences in blood parameters between the groups, and no abnormal clinical findings. Two dogs treated with six times the RTD vomited, but no vomiting was observed when administration was repeated two days later.     

Efficacy of licofelone in dogs with clinical osteoarthritis

To evaluate the effect of licofelone, an arachidonic acid substrate with combined inhibitory activity against 5-lipoxygenase and cyclooxygenases 1 and 2, a double-blind, randomised and placebo-controlled study was conducted in 33 client-owned dogs that were lame owing to hindlimb osteoarthritis. Seventeen of the dogs received a placebo and 16 were treated with 2.5 mg/kg licofelone twice a day for 28 days. The dogs' lameness was assessed on a visual analogue scale (vas), and by force plate analyses at baseline and 14 and 28 days after starting the treatment. After 14 days the mean (se) change in peak vertical force in the licofelone-treated dogs (1.7 [0.8] per cent bodyweight) was significantly greater (P<0.05) than in the placebo-treated dogs (-0.3 [0.6] per cent bodyweight), and after 28 days the difference had increased. In contrast, the dogs' lameness, as assessed by the vas values, had decreased significantly over baseline in both the treated and control groups.     

Firocoxib efficacy preventing urate-induced synovitis, pain, and inflammation in dogs

This positive-control study evaluated the efficacy of firocoxib versus carprofen, deracoxib, and meloxicam for the prevention of pain and inflammation in a urate crystal synovitis model of lameness. Lameness scoring and force plate gait analysis were used to assess efficacy. The resulting lameness scores and force plate ground reaction forces after urate crystal injection were not significantly different among the groups. Relative to each group's baseline (nonlame) score, only the firocoxib group was not significantly lame, based on lameness score, at the model's peak effect.     

Pharmacokinetics and clinical efficacy of a cinchophen and prednisolone combination in the dog

The kinetics and efficacy of a cinchophen prednisolone combination preparation (PLT) were assessed in the dog. Cinchophen administered at a dose rate of 12-5 mg/kg intravenously had a volume of distribution (Vd area) of 0–13 litres/kg, a clearance rate (Cl) of 0–15 litres/h and a half-life (t _1/2β of 7–92 hours. Following oral administration the bioavailability was 87-21 per cent. Prednisolone administered at a dose rate of 0–15 mg/kg intravenously had a Vd area of 2–7 litres/kg, a CI of 0–116 litres/h and a t_1/2β of 1–11 hours. PLT given to dogs with osteoarthritis at a dosage range of between 25 and 44 mg/kg per day cinchophen and between 0–125 and 0–220 mg/kg per day prednisolone for a maximum of 14 days significantly improved lameness (P<0–001), weight bearing (P<0–005), joint mobility (P<0–01) and stiffness (P<0–001) scores and was similar in clinical efficacy to phenylbutazone.     

Long-term treatment with carprofen of 805 dogs with osteoarthritis

The pain-relieving effect of carprofen and tolerance to the drug were investigated in 805 dogs that were lame as a result of osteoarthritis. The dogs were of different breeds, ages and bodyweights and of both sexes, and were selected from 51 veterinary clinics. Each dog was treated orally by its owner with 4 mg/kg carprofen for 84 consecutive days. Twenty-four dogs were removed from the study because of side effects, and 55 left the study for reasons unrelated to the treatment. The condition of the dogs and the benefit of the treatment were evaluated by the veterinary surgeons and the owners after 14 days, and at the end of the period of treatment, when 194 of the dogs (26.7 per cent) were no longer lame, and 357 (49.2 per cent) had improved. The period for which the dogs had been lame before entering the study significantly (P<0.01) affected the results and the rate of improvement. Too much exercise during the 84 days of treatment caused some dogs to relapse.     

Reduced dosage of ketoprofen for the short-term and long-term treatment of joint pain in dogs

Two studies were conducted under laboratory conditions with 16 dogs to investigate the analgesic effectiveness of a low dose of ketoprofen in a short-term sodium urate crystal-induced synovitis model of arthritis. The effect of the treatment, defined as the improvement in peak vertical force weight bearing was evaluated in the first study at three dose levels. A single oral dose of 0.25 mg/kg ketoprofen was significantly better (P < 0.01) than the control (0 mg), but doses of 0.5 and 0.75 mg/kg did not improve the dogs' weight bearing further. The second study investigated the efficacy and safety of the 0.25 mg/kg dose administered daily for 30 days. The beneficial effects of ketoprofen at this dose were constant, with the treated dogs bearing 89.1 per cent of the baseline vertical force four hours after the induction of arthritis on day 1 and 92.2 per cent on day 29, compared with 42 per cent and 34 per cent of the baseline in the untreated dogs. No gastrointestinal or other side effects were observed during the treatment.     

Evaluation of adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs

OBJECTIVE: To evaluate adverse effects of long-term oral administration of carprofen, etodolac, flunixin meglumine, ketoprofen, and meloxicam in dogs. ANIMALS: 36 adult dogs. PROCEDURES: Values for CBC, urinalysis, serum biochemical urinalyses, and occult blood in feces were investigated before and 7, 30, 60, and 90 days after daily oral administration (n = 6 dogs/group) of lactose (1 mg/kg, control treatment), etodolac (15 mg/kg), meloxicam (0.1 mg/kg), carprofen (4 mg/kg), and ketoprofen (2 mg/kg for 4 days, followed by 1 mg/kg daily thereafter) or flunixin (1 mg/kg for 3 days, with 4-day intervals). Gastroscopy was performed before and after the end of treatment. RESULTS: For serum gamma-glutamyltransferase activity, values were significantly increased at day 30 in dogs treated with lactose, etodolac, and meloxicam within groups. Bleeding time was significantly increased in dogs treated with carprofen at 30 and 90 days, compared with baseline. At 7 days, bleeding time was significantly longer in dogs treated with meloxicam, ketoprofen, and flunixin, compared with control dogs. Clotting time increased significantly in all groups except those treated with etodolac. At day 90, clotting time was significantly shorter in flunixin-treated dogs, compared with lactose-treated dogs. Gastric lesions were detected in all dogs treated with etodolac, ketoprofen, and flunixin, and 1 of 6 treated with carprofen. CONCLUSIONS AND CLINICAL RELEVANCE: Carprofen induced the lowest frequency of gastrointestinal adverse effects, followed by meloxicam. Monitoring for adverse effects should be considered when nonsteroidal anti-inflammatory drugs are used to treat dogs with chronic pain.     

Evaluation of a human generic formulation of ciclosporin in the treatment of canine atopic dermatitis with in vitro assessment of the functional capacity of phagocytic cells

To compare the efficacy, tolerability and safety of a generic formulation of ciclosporin for human beings with prednisone in the treatment of canine atopic dermatitis), human generic ciclosporin A (hgCsA) (5 mg/kg daily) and prednisone (1 mg/kg daily for seven days, followed by 1 mg/kg every second day) were administered to 13 and seven dogs with atopic dermatitis, respectively, for 42 days. Skin changes were assessed using a modified canine atopic dermatitis extent and severity index (mCADESI-01) and a pruritus intensity scale system. The in vitro functional capacity of phagocytic cells was assessed using the tetrazolium reductase activity and zymosan-stimulated tetrazolium reductase activity tests, as well as measurements of the percentage phagocytic activity and the ingestion capacity of phagocytic cells. Haematological and biochemical parameters were also monitored. There was a greater than or equal to 50 per cent reduction from the baseline in mCADESI-01 scores in 84.6 and 100 per cent of dogs, and a greater than or equal to 50 per cent reduction from the baseline in pruritus scores in 76.9 and 85.7 per cent of dogs, treated with hgCsA and prednisone, respectively. No important adverse physical, haematological or biochemical effects occurred with either drug and no statistically significant changes were detected in any of the four tests assessing the functional activity of phagocytes. The generic formulation of ciclosporin was effective in reducing the severity of physical signs of canine atopic dermatitis and was well tolerated.     

Effect of deracoxib,a new COX-2 inhibitor,on the prevention of lameness induced by chemical synovitis in dogs

Twenty-four healthy, mixed-breed hound-type dogs were evenly and randomly assigned to a placebo control group, one of four dosages of deracoxib (0.3, 1, 3, or 10 mg/kg), or carprofen (2.2 mg/kg). Oral dosing of placebo, carprofen, or deracoxib was done 30 minutes before intraarticular injection of urate crystal suspension for induction of synovitis. Ground reaction forces, subjective clinical lameness scores, pain, joint effusion, and quantitative pain threshold responses were measured in a blinded fashion before induction of synovitis and 2, 4, 6, 8, 12, and 24 hours after injection. The medium and high dosages of deracoxib were effective in preventing lameness and pain associated with synovitis. Carprofen was also somewhat effective in attenuating the severity of urate-induced synovitis but to a lesser degree than the medium dose of deracoxib. Preemptive deracoxib treatment at dosages as low as 1 mg/kg reduced lameness and pain of synovitis associated with intraarticular administration of urate crystals.     

Field Trial Validation of the Efficacy and Acceptability of Firocoxib,a Highly Selective Cox-2 Inhibitor,in a Group of 96 Lame Horses

The objective was to generate evidence for clinical efficacy and acceptability of a second generation coxib, firocoxib, administered orally for 14 days to lame horses under field conditions compared with a classic nonsteroidal anti-inflammatory drug, vedaprofen, in a prospective, randomized, controlled, double-blinded, multicenter field trial. Ninety-six client-owned horses with American Association of Equine Practitioners score of at least grade 3 lameness or grade 2 lameness plus at least a score of 2 for either pain on palpation, range of motion, or joint swelling were analyzed. Horses were administered 0.1 mg/kg firocoxib orally at 24 hour intervals (n = 48) or 1.0 mg/kg vedaprofen paste at 12 hour intervals for 14 days (single loading dose of 2.0 mg/kg vedaprofen) (n = 48). Physical examinations and lameness evaluations were conducted on Day 1 (V1, before treatment) and on Days 7 (V2) and 14 (V3). Blood chemistry and hematology profiles were also evaluated. With regard to the primary variable, clinical improvement, 83% of the firocoxib-treated horses improved at V3 compared with 65% of vedaprofen-treated horses improved meeting the criteria defined to demonstrate noninferiority of firocoxib to vedaprofen. Health and behavioral abnormalities for side effect detection occurred at the rate of 2% (1 horse) and 8% (4 horses) for firocoxib- and vedaprofen-treated horses, respectively. Changes in hematology and blood chemistry values from V1 to V3 were not significantly different between treatment groups. Firocoxib, formulated as an oral paste was highly effective, well tolerated, and acceptable for the control of pain and inflammation associated with lameness in horses under field conditions.     

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 analgesic efficacy of preoperative or postoperative carprofen with or without preincisional mepivacaine epidural anesthesia in canine pelvic or femoral fracture repair

Objective— To compare analgesic efficacy of preoperative versus postoperative administration of carprofen and to determine, if preincisional mepivacaine epidural anesthesia improves postoperative analgesia in dogs treated with carprofen. Study Design— Blind, randomized clinical study. Animals— Dogs with femoral (n=18) or pelvic (27) fractures. Methods— Dogs were grouped by restricted randomization into 4 groups: group 1=carprofen (4 mg/kg subcutaneously) immediately before induction of anesthesia, no epidural anesthesia; group 2=carprofen immediately after extubation, no epidural anesthesia; group 3=carprofen immediately before induction, mepivacaine epidural block 15 minutes before surgical incision; and group 4=mepivacaine epidural block 15 minutes before surgical incision, carprofen after extubation. All dogs were administered carprofen (4 mg/kg, subcutaneously, once daily) for 4 days after surgery. Physiologic variables, nociceptive threshold, lameness score, pain, and sedation (numerical rating scale [NRS], visual analog scale [VAS]), plasma glucose and cortisol concentration, renal function, and hemostatic variables were measured preoperatively and at various times after surgery. Dogs with VAS pain scores >30 were administered rescue analgesia. Results— Group 3 and 4 dogs had significantly lower pain scores and amount of rescue analgesia compared with groups 1 and 2. VAS and NRS pain scores were not significantly different among groups 1 and 2 or among groups 3 and 4. There was no treatment effect on renal function and hemostatic variables. Conclusions— Preoperative carprofen combined with mepivacaine epidural anesthesia had superior postoperative analgesia compared with preoperative carprofen alone. When preoperative epidural anesthesia was performed, preoperative administration of carprofen did not improve postoperative analgesia compared with postoperative administration of carprofen. Clinical Relevance— Preoperative administration of systemic opioid agonists in combination with regional anesthesia and postoperative administration of carprofen provides safe and effective pain relieve in canine fracture repair.     

Comparison of the activity of selamectin, imidacloprid and fipronil for the treatment of dogs infested experimentally with Ctenocephalides canis and Ctenocephalides felis felis.

Twenty-four beagles were randomly allocated into four groups of six and housed in separate cages. Each dog was infested with 25 Ctenocephalides canis and 25 Ctenocephalides felis felis and two days later (day 0) the dogs in groups 1, 2 and 3 received a spot-on application of selamectin (6 mg/kg), imidacloprid (10 mg/kg), or fipronil (6-7 mg/kg), respectively, while the dogs in group 4 were not treated. The dogs were combed 48 hours later, the fleas were removed, counted and their species were determined. All the dogs were reinfested with the same number of the two species of fleas on days 7, 14, 21, 28 and 35, and the efficacy of the treatments was calculated 48 hours after each infestation. The mean numbers of fleas on the control dogs were 19.8 C. canis and 14.7 C. felis felis. The three treatments were effective for the full 35 days of the trial; over the first 28 days, the efficacy of selamectin ranged from 81 to 100 and 92 to 99 per cent against C. felis felis and C canis, respectively, the efficacy of imidacloprid ranged from 98 to 100 per cent and the efficacy of fipronil was 100 per cent against both species. There were no significant differences between the three treatments.     

Efficacy of nitenpyram as a systemic flea adulticide in dogs and cats

In a clinical trial involving 123 cats and 88 dogs, the efficacy of tablets containing nitenpyram against natural flea infestations was investigated. The animals were selected from the routine cases of nine veterinary clinics in the UK and 143 were treated with the tablets and 68 control animals were treated with placebo tablets. Each animal was maintained in an individual cage. The time when the first fleas fell off each animal was recorded between 30 minutes and five hours after treatment, and six hours after treatment the numbers of live, moribund or dead fleas on each animal were determined, and the flea survival rate was calculated. The drug's efficacy was assessed by comparing the mean survival rates of fleas on the treated and control animals. Fleas started to fall from the animals 30 minutes after treatment and two hours after treatment some fleas had detached from 81 per cent of the treated animals. After six hours the efficacy of the drug reached 96.7 per cent on dogs and 95.2 per cent on cats, and 85.9 per cent of the fleas were found off the treated animals, compared with 1.8 per cent in the controls. No adverse drug reactions were recorded during the trial.