Investigation on the clinical efficacy and safety of meloxicam (Metacam) in the treatment of non-infectious locomotor disorders in pigs

The clinical efficacy and safety of meloxicam (Metacam 20 mg/ml) in the treatment of non-infectious locomotor disorders in pigs was investigated in a randomised double-blind, placebo controlled, multi-centre field study. A total of 220 pigs were examined, 211 pigs were suitable for evaluation. Treatment was performed on Day 1 with meloxicam (0.4 mg meloxicam/kg) or placebo by intramuscular injection. If necessary, treatment was optionally repeated on Day 2. Clinical examinations were conducted daily from Day 1 (immediately prior to initiation of therapy) to Day 4. The primary parameter, mean "Clinical Lameness Score" (CLS, a sum of the scores of "Lameness at Rest" and "Lameness at Walk"; range 2 to 11) improved from 6.8 and 6.3 on Day 1, to 3.5 and 4.7 on Day 4 in the meloxicam and placebo groups respectively (p < 0.001). At the final examination mean changes from baseline for CLS (Day 1) were 3.25 for meloxicam treated animals and 1.7 for placebo treated animals (p < 0.001). Behaviour score and feed intake improved during the study period with statistically significant differences in favour of meloxicam at all time points after initiation of therapy. Significantly fewer pigs received a second treatment in the meloxicam group than in the placebo group, 46% versus 73% (p < 0.001). A 'very good' or 'good' clinical efficacy assessment was recorded in 83% of the meloxicam cases compared to 42% of the placebo controls at the final examination (p < 0.001). No adverse events were reported due to the use of meloxicam. Furthermore safety of meloxicam in pregnant sows was demonstrated. It is concluded that intramuscular injection of meloxicam (Metacam) at a dosage of 0.4 mg/kg is efficacious and safe for the treatment of non-infectious locomotor disorders in pigs.     

Clinical efficacy of diclofenac sodium and flunixin meglumine as adjuncts to antibacterial treatment of respiratory disease of calves

Objective To compare the efficacy of the non-steroidal antiinflammatory drugs, diclofenac sodium and flunixin meglumine as adjuncts to the antibiotic treatment of bovine respiratory disease (BRD). Procedure We randomly allocated 80 Holstein calves with BRD to three groups. All the calves received a dose of 2.5 mg/kg tulathromycin by single subcutaneous injection and two of the groups received, in addition, either 2.5 mg/kg diclofenac sodium as a single intramuscular injection (diclofenac group, n = 30) or 2.2 mg/kg flunixin meglumine as an intravenous injection on the first three consecutive days after tulathromycin administration (flunixin group, n = 30). All calves were given a clinical score prior to initial treatment (day 0) and after treatment (days 1, 2, 3, 7 and 14) by observing appetite, demeanour, rectal temperature, the rate and type of respiration, presence or absence of coughing, and nasal discharge. Results During the first 48 h, improvement of adverse signs of respiratory disease, such as pyrexia and elevated respiratory rate, and of a high clinical index score was significant in the two adjunct groups compared with the calves receiving antibiotic alone. The reduction in pyrexia was greatest in the diclofenac group. There were no statically significant differences between treatment groups with regard to eventual perceived recovery from respiratory disease in 14 days. Conclusion In this trial, a single intramuscular dose of diclofenac sodium was equally effective as three intravenous injections of flunixin meglumine given on consecutive days as adjunctive therapy for BRD.     

Effects of the cyclooxygenase inhibitor meloxicam on recovery of ischemia-injured equine jejunum

OBJECTIVE: To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum. ANIMALS: 18 horses. PROCEDURES: Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed. RESULTS: Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects. CONCLUSIONS AND CLINICAL RELEVANCE: Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.     

A comparative study of the effects of meloxicam and flunixin meglumine (NSAIDs) as adjunctive therapy on interferon and tumor necrosis factor production in calves suffering from enzootic bronchopneumonia

The study was performed on 18 Black-and-White Lowland Breed calves with clinical signs of enzootic bronchopneumonia divided into three groups and respectively treated with oxytetracycline and meloxicam--Group I (9 animals); oxytetracycline and flunixin meglumine--Group II (3 animals); and oxytetracycline only--Group III (6 animals--control). The following observations were recorded before treatment (1st day) and two days later (3rd day): body temperature, the serum level of interferon (IFN) and tumor necrosis factor (TNF) as well as cytokine production by bronchoalveolar lavage (BAL) cells. The treatment of calves with a combination of oxytetracycline and meloxicam (Group I) and especially with oxytetracycline and flunixin meglumine (Group II) caused a significantly faster, in comparison to the control group, normalization of body temperature. Both drugs, meloxicam and especially flunixin meglumine, inhibited excessive TNF production in the organism (measured as the serum level of cytokine). Moreover, BAL cells isolated from calves treated with both NSAIDs were still able, ex vivo, to release TNF, in contrast to the control group (treated only with tetracycline) which lost the ability to produce TNF. The treatment of the calves with meloxicam and flunixin meglumine did not significantly influence the levels of IFN in sera but normalized ex vivo IFN production in BAL cells. These results suggest that the combination of meloxicam with an antibiotic or flunixin meglumine with an antibiotic which does not exert an immunosuppressive influence on the organism of calves suffering from enzootic bronchopneumonia is equally effective in the treatment of calves and superior to the antibiotic alone.     

Comparison of carprofen and flunixin meglumine asadjunctive therapy in bovine respiratory disease

In an open, controlled, multi-centre clinical field trial, seven ‘naturally occurring’ outbreaks of acutefebrile (rectal temperature ≥ 39·5°C) respiratory disease in housed calves were treated with a single antimicrobial agent, and either the non-steroidal anti-inflammatory drug (NSAID) carprofen (n=95) or flunixin meghunine (n=92) on an alternate basis. Carprofen was administered as a single subcutaneous injection at a mean dosage of 1·4 mg kg⁻¹ (range 1·2 to 1·9 mg kg⁻¹) body weight on the first day and flunixin meglumine by intravenous injection at a mean dosage of 2·0 mg kg⁻¹ (range 1·2 to 2·6 mg kg⁻¹) body weight on the first 3 consecutive days. All calves were examined clinically immediately prior to initial treatment and on three occasions up to 1 week after the end of treatment. There were no statistically significant differences between NSAID groups in reduction of clinical parameters between examinations, or in overall efficacy. This trial demonstrated that a single dose of carprofen was equally effective as three daily closes of flunixin meglumine as adjunctive therapy to antimicrobial treatment in acute respiratory disease in calves.     

Long-term effects of meloxicam in the treatment of respiratory disease in fattening cattle

The long-term effects of a single dose of meloxicam (Metacam 20 mg/ml; Boehringer Ingelheim Vetmedica) in conjunction with antibiotic therapy in cattle with clinical signs of bovine respiratory disease (BRD) was evaluated in a blind, controlled, randomised study. Two hundred animals with clinical signs of brd received a single subcutaneous injection of 20 mg/kg oxytetracycline; 100 of them also received a subcutaneous injection of 0.5 mg/kg meloxicam, and the other 100 received an injection of isotonic saline. The animals were weighed before they were treated and seven, 35, 70 and 105 days later, and finally before they were slaughtered. The mean bodyweight of the meloxicam-treated animals was significantly higher from day 70 until slaughter, and the mean average daily weight gain until slaughter and the mean carcase weight of the animals treated with meloxicam were significantly higher. In the animals with lung lesions, significantly less lung tissue was affected in those that had been treated with meloxicam.     

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.     

Effects of adrenocorticotropic hormone and flunixin meglumine on pregnancy retention in beef cows

Pregnancy loss in beef cattle after d 28 of gestation is variable, but it has been reported to be as great as 14% and has been related to transportation or handling stress. The primary objective of this study was to determine whether activation of the hypophyseal-adrenal axis with ACTH would mimic a stressful response and cause pregnancy loss in beef cattle. A secondary objective was to determine if a single injection of the PG synthesis inhibitor flunixin meglumine would attenuate the stress response and suppress serum PGF(2α) concentrations to prevent pregnancy loss. Forty nonlactating beef cows that were 34 ± 0.33 d pregnant were used for this study. In a 2 × 3 factorial arrangement, cows were randomly assigned to receive ACTH [0 or 0.5 IU/kg of BW, intramuscularly (i.m.)] at 0 and 2 h of the study and flunixin meglumine (0, 1.1, or 2.2 mg/kg of BW, i.m.) at 0 h. Blood samples were collected from all cows at 0 h and every 30 min for 4 h to measure serum cortisol and PGF(2α) metabolite (PGFM) concentrations. Rectal temperature was collected for each cow at 0, 120, and 240 min. Pregnancy exams were conducted 31 and 58 d after treatment by transrectal ultrasonography, and the presence of a fetal heartbeat was used as an indicator of fetal viability. Serum cortisol concentration was affected (P < 0.01) by ACTH, time, and the interaction of ACTH × time, but not by flunixin meglumine (P ≥ 0.14) or any other interactions. Cortisol concentrations increased (P < 0.01) in the serum of ACTH-treated cows immediately after ACTH treatment and remained increased (P < 0.01) throughout the 4-h sampling period. Serum PGFM concentration was not affected by ACTH (P = 0.97) or by any interactions (P > 0.35) with ACTH, but was affected (P < 0.01) by flunixin meglumine, time, and the interaction of flunixin meglumine × time. Regardless of dosage (1.1 or 2.2 mg/kg of BW), flunixin meglumine decreased (P < 0.01) serum PGFM concentrations in both ACTH-treated and control cows for the duration of the study. Although ACTH treatment induced a prolonged increase in serum cortisol concentration, none of the cows used in this study lost a pregnancy. In conclusion, the activation of the hypophyseal-adrenal axis with ACTH increased serum cortisol concentrations but did not increase serum concentrations of PGFM or cause pregnancy loss during early gestation in cows. Flunixin meglumine treatment suppressed serum PGFM concentrations in control and ACTH-treated cows.     

Evaluation of the influence of meloxicam and flunixin meglumine on the apoptosis of peripheral blood CD4+ and CD8+ T cells in calves

The aim of the study was to determine whether treatment with recommended doses of meloxicam or flunixin had an effect on the apoptosis of peripheral blood T lymphocytes in calves. The study was carried out on 4-5 months old calves (n = 24, 8 per group). Experimental animals were injected subcutaneously with a single dose of 0.5 mg x kg(-1) of meloxicam or intravenously with 3 doses of 2.2 mg x kg(-1) day(-1) of flunixin. The non-treatment animals served as control. Blood samples were taken at day 0 and at days 1, 2, 3, 5, 7 and 14 after the first NSAIDs injection. Apoptosis was determined by flow cytometry using Annexin V-PE/7-AAD staining. The kinetic analysis of apoptosis in the total lymphocyte population, as well as in the CD4+ and CD8+ subsets did not reveal significant differences in the frequency of early apoptotic cells between control and experimental groups throughout the period studied. Although, 24 h after administration of the first dose of NSAIDs, late-stage apoptosis/necrosis was significantly increased in the total lymphocyte population (the meloxicam group), as well as in the CD4+ (the meloxicam group and the flunixin group) and CD8+ (the flunixin group) subsets of T cells. However, this disturbance was transient, relatively poorly expressed and, thus, unlikely to be of clinical significance. Our results indicate that the use of meloxicam or flunixin in accordance with the recommended dosage regimen in cattle do not have a clinically significant influence on apoptosis of peripheral blood T cells.     

Comparative evaluation of two ivermectin injectable formulations against psoroptic mange in feedlot cattle

A study was carried out to compare the efficacy of two injectable formulations of ivermectin, Ivomec,(1) Merial (IVM reference) and Ivogell,(2) Intervet (IVM generic) in the treatment of psoroptic mange (Psoroptes ovis) in Charollais feedlot cattle. A total of 22 animals were ranked in order of the severity of mange and allocated to 11 replicates of 2 animals each. Within each replicate, one animal was randomly allocated to IVM reference product treatment (Group 1) and one to IVM generic (Group 2). Animals were treated on Day 0 and on Day 8 at the recommended dosage of 200 microg ivermectin/kg bodyweight. The pharmacokinetics profiles (pK) of both IVM formulations were evaluated in plasma samples taken from 6 cattle randomly chosen per group on Day 0, before treatment, and then at 6, 12, 24 hours and daily from Day 2 to Day 7 after the treatment on Day 0. Additionally, the severity of mange lesions was assessed and mites were counted in skin scrapings on Days 0, 8, 15 and 25. Animals were weighed on Day 0 and 25 and body weight and average daily gains (ADG) were evaluated. No statistical differences were found between the cattle of the two groups in any pK parameters, although the mean IVM plasma concentrations in cattle treated with the IVM reference product were consistently higher than those found in cattle treated with the generic compound. By Day 25, all animals in Group 1 had recovered clinically and parasitologically from psoroptic mange while cattle from Group 2 still had mange lesions and, in two animals, living mites were found in the skin scrapings; these differences were significant (P<0.001). The mean body weight of the two groups was significantly different on Day 25 (P<0.01) when animals in Group 1 weighed 20 kg more than those in Group 2. In conclusion, despite similarities in their pharmacokinetic profiles and formulations, the clinical efficacy of the two injectable formulations of IVM differed significantly in their therapeutic efficacy against psoroptic mange in feedlot cattle up to 25 days after treatment: this difference in response was reflected in an incomplete clinical and parasitological response in Group 2 and a slower growth rate.     

Effect of Meloxicam Treatment during Early Pregnancy in Holstein Heifers

We previously reported that administration of flunixin meglumine two times at a critical stage approaching pregnancy recognition associated with maintenance of the corpus luteum (CL) increased early embryo survival and pregnancy rate via an additive antiluteolytic effect with the conceptus [Vet Rec 160 (2007) 404]. In this study, the objective was to determine if a single administration of meloxicam, a non‐steroid anti‐inflammatory drug with a longer half‐life, could be used instead of flunixin meglumine. This would avoid repeated injections in heifers following insemination at a critical stage to increase pregnancy rate due to its inhibitory effect on prostaglandin F_2α synthesis. Eighty‐five, 15‐ to 18‐month‐old Holstein heifers were synchronized, and following insemination (day 0) heifers were assigned to receive subcutaneous meloxicam injection (0.5 mg/kg; n = 37) on the afternoon of day 15 or were untreated as a control (n = 48). Pregnancy rates were defined as the percentage of heifers inseminated that were diagnosed pregnant by ultrasound between days 31 and 38 after artificial insemination. Effect of the treatment on pregnancy rates was analysed by chi‐square test. Meloxicam treatment on day 15 after insemination dramatically decreased pregnancy rates in the heifers (52%; 25 of 48 in the control group vs 24.3%; 9 of 37 in the meloxicam‐treated group; p < 0.01). This result indicates that administration of meloxicam at the time associated with pregnancy recognition processes to maintain the CL was harmful to the pregnancy even though the drug is considered to be safe during pregnancy in cattle.     

Clinical evaluation of meloxicam versus ketoprofen in cats suffering from painful acute locomotor disorders

The aim of this study was to evaluate the efficacy and palatability of meloxicam 0.5mg/ml oral suspension, compared to ketoprofen tablets in cats suffering from painful acute locomotor disorders. This single blinded, positively-controlled, randomised, multicentre trial involved 121 client owned cats. Cats received either meloxicam (0.5mg/ml oral suspension) at 0.1mg/kg on day 1 followed by 0.05mg/kg q 24h on days 2-5, or ketoprofen 5mg tablets at 1.0mg/kg q 24h for 5 days. The efficacy of the two treatments was assessed subjectively by clinicians on day 6 using a clinical sum score (CSS). Palatability and accuracy of dosing were also assessed. The baseline CSS was not significantly different between the groups, and after 5 days of treatment the CSS had decreased to a similar extent, reflecting a reduction in pain. There were no significant differences between the CSS of each group at day 6. Both treatments were well tolerated. Meloxicam was significantly more palatable than ketoprofen, and allowed for more accurate dosing. Meloxicam and ketoprofen are a safe and efficacious treatment for acute locomotor disorders in cats. Meloxicam (Metacam) may be associated with superior compliance in clinical practice due to the higher palatability, which results in better ease of administration.     

Evaluation of flunixin meglumine as an adjunct treatment for diarrhea in dairy calves

OBJECTIVE: To assess the use of flunixin meglumine as an adjunct treatment for diarrhea in calves. DESIGN: Clinical trial. ANIMALS: 115 calves with diarrhea that were 1 to 21 days old at enrollment. PROCEDURE: Calves that developed diarrhea were randomly assigned to receive no flunixin meglumine (controls), a single dose of flunixin meglumine (2.2 mg/kg [1.0 mg/lb]), or 2 doses of flunixin meglumine administered 24 hours apart. Serum IgG concentration and PCV were measured prior to enrollment in the trial. Calves were evaluated daily to determine rectal temperature, fecal consistency, demeanor, and skin elasticity score. The primary analytic outcome was days of sickness (morbid-days). RESULTS: Calves with fecal blood and treated with a single dose of flunixin meglumine had fewer morbid-days and antimicrobial treatments, compared with controls. Although not significant, calves given 2 doses of flunixin meglumine in 24 hours had fewer morbid-days than untreated control calves. Regardless of severity of diarrhea, calves without fecal blood did not benefit from the use of flunixin. For calves with fecal blood, failure of passive transfer (low serum IgG concentration) was an independent risk factor for increased morbid-days. CONCLUSIONS AND CLINICAL RELEVANCE: Treatment with a single dose of flunixin meglumine resulted in fewer antimicrobial treatments and morbid-days in calves with fecal blood. As observed in other studies, calves with failure of passive transfer were at high risk for poor outcomes. This emphasizes the importance of developing and implementing effective colostrum delivery programs on dairy farms.     

Feedlot performance of steers treated concurrently with ceftiofur crystalline-free acid subcutaneously in the posterior aspect of the ear and a growth-promoting implant

Ceftiofur crystalline-free acid sterile suspension (CCFA-SS), a long-acting formulation of ceftiofur formulated for subcutaneous injection in the middle third of the posterior aspect of the ear, is being developed for the control and treatment of bovine respiratory disease. A study was designed to evaluate average daily gain (ADG) and feed efficiency (FE) for cattle through 140 days in the feedlot after CCFA-SS was administered concurrently in the same ear with a growth-promoting implant. On Day 0, steers (n = 207) averaging 189 kg in weight were randomly assigned to the following treatments: Revalor -S implant (120 mg trenbolone acetate and 24 mg estradiol per implant; Hoechst-Roussel Agri-Vet Company) (n = 64); CCFA-SS at 6.6 mg ceftiofur equivalents/kg and a Revalor -S implant (n = 64); untreated control (no CCFA-SS or implant) (n = 63); or CCFA-SS only (n = 16). On Day 56, an Implus-S implant (200 mg progesterone USP plus 20 mg estradiol benzoate; Pharmacia and Upjohn Animal Health) was administered to all cattle. Tolerance of administration of all materials was observed visually and by palpation of the treated ears. Average daily gain and FE from Day 0 through Day 56 were significantly (P <.001) better for steers of both groups with an implanted growth-promotant than for untreated controls. From Day 0 through Day 140, ADG was significantly (P <.05) better for cattle given an implant or an implant plus CCFA-SS than for untreated controls and FE was significantly (P <.05) better for cattle given an implant plus CCFA-SS than for controls. Mild or moderate, transient swelling of the treated ear was observed in two cattle (CCFA-SS plus implant) on Day 52. On Day 56, 88 % of cattle treated with CCFA-SS, 84 % of the cattle treated with an implant plus CCFA-SS, and 100 % of cattle in other groups were normal. Administration of CCFA-SS in the middle third of the posterior aspect of the ear at the same time as growth-promoting implants did not affect performance of cattle in the feedlot and was well tolerated by the animals.     

Effects of phenylbutazone alone or in combination with flunixin meglumine on blood protein concentrations in horses

OBJECTIVE: To assess effects of treatment with phenylbutazone (PBZ) or a combination of PBZ and flunixin meglumine in horses. ANIMALS: 24 adult horses. PROCEDURE: 13 horses received nonsteroidal antiinflammatory drugs (NSAIDs) in a crossover design. Eleven control horses were exposed to similar environmental conditions. Treated horses received PBZ (2.2 mg/kg, PO, q 12 h, for 5 days) and a combination of PBZ and flunixin meglumine (PBZ, 2.2 mg/kg, PO, q 12 h, for 5 days; flunixin meglumine, 1.1 mg/kg, IV, q 12 h, for 5 days). Serum samples were obtained on day 0 (first day of treatment) and day 5, and total protein, albumin, and globulin were measured. RESULTS: 1 horse was euthanatized with severe hypoproteinemia, hypoalbuminemia, and colitis during the combination treatment. Comparisons revealed no significant difference between control horses and horses treated with PBZ alone. There was a significant difference between control and treated horses when administered a combination of PBZ and flunixin meglumine. Correction for horses with values >2 SDs from the mean revealed a significant difference between control horses and horses administered the combination treatment, between control horses and horses administered PBZ alone, and between horses receiving the combination treatment and PBZ alone. Gastroscopy of 4 horses revealed substantial gastric ulcers when receiving the combination NSAID treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of results of the study indicates the need for caution when administering a combination NSAID treatment to horses because the detrimental effects may outweigh any potential benefits.     

Flunixin meglumine in calves with natural bovine respiratory syncytial virus infection

Twenty-three calves (three to eight months of age) with serological evidence of bovine respiratory syncytial virus infection were used in this study. The calves originated from four herds with respiratory tract disease. In a double blind trial the calves were injected intravenously with either flunixin meglumine (2 mg/kg body weight) or with a placebo. The effect on the course of disease was measured using the PO2 in capillary blood samples from the ears of the calves and by the effect on body temperature and respiratory rate. Mean body temperature fell significantly in the flunixin meglumine treated group. Statistically significant differences were not found between the treated and control group during the seven-day examination period.     

Distribution of flunixin meglumine and firocoxib into aqueous humor of horses

Background: Nonsteroidal anti‐inflammatory drugs (NSAIDs) are commonly used systemically for the treatment of inflammatory ocular disease in horses. However, little information exists regarding the ocular penetration of this class of drugs in the horse. Objective: To determine the distribution of orally administered flunixin meglumine and firocoxib into the aqueous humor of horses. Animals: Fifteen healthy adult horses with no evidence of ophthalmic disease. Methods: Horses were randomly assigned to a control group and 2 treatment groups of equal sizes (n = 5). Horses assigned to the treatment groups received an NSAID (flunixin meglumine, 1.1 mg/kg PO q24h or firocoxib, 0.1 mg/kg PO q24h for 7 days). Horses in the control group received no medications. Concentrations of flunixin meglumine and firocoxib in serum and aqueous humor and prostaglandin (PG) E₂ in aqueous humor were determined on days 1, 3, and 5 and aqueous : serum ratios were calculated. Results: Firocoxib penetrated the aqueous humor to a significantly greater extent than did flunixin meglumine at days 3 and 5. Aqueous : serum ratios were 3.59 ± 3.32 and 11.99 ± 4.62% for flunixin meglumine and firocoxib, respectively. Ocular PGE₂ concentrations showed no differences at any time point among study groups. Conclusions and Clinical Importance: Both flunixin meglumine and firocoxib penetrated into the aqueous humor of horses. This study suggests that orally administered firocoxib penetrates the aqueous humor better than orally administered flunixin meglumine at label dosages in the absence of ocular inflammation. Firocoxib should be considered for the treatment of inflammatory ophthalmic lesions in horses at risk for the development of adverse effects associated with nonselective NSAID administration.     

The effect of estradiol cypionate (ECP) on ovarian follicular development and ovulation in dairy cattle.

The efficacy of estradiol cypionate (ECP) for synchronizing ovarian follicular development was determined in lactating Holstein-Friesian cattle. In Experiment 1, 13 cattle were given simultaneous intramuscular (i.m.) injections of 100 mg progesterone and 0 (control), 0.5 or 1.0 mg ECP on Day 3, after a synchronized ovulation (Day 0). Maximum diameter of the dominant follicle of Wave 1 was significantly larger in control cattle than in those given 0.5 or 1.0 mg ECP (means: 15.7, 13.2, and 12.9 mm, respectively). Mean day of emergence of Wave 2 was significantly later in controls than in those given 1.0 mg ECP, with the 0.5 mg group intermediate (Days 10.2, 8.8 and 9.5, respectively). In Experiment 2, 14 cattle were given a CIDR-B and IM injections of 1 mg ECP and 50 mg progesterone without regard to stage of cycle (treatment = Day 0). On Day 8, the CIDR-B was removed and 500 micrograms cloprostenol injected, IM. Mean days of wave emergence (Day 3.4; range: -2 to 7) and ovulation (Day 12.1; range: 10 to 14) indicated that ECP had limited efficacy for synchronizing follicular development and ovulation in dairy cattle when given at random stages of the estrous cycle.     

Efficacy and safety of 3 versus 5 days of meloxicam as an analgesic for feline onychectomy and sterilization

Three- or 5-day courses of meloxicam [0.2 mg/kg body weight (BW) subcutaneously pre- or postoperatively on Day 1 followed by 0.05 mg/kg BW, PO per day thereafter] were assessed for analgesic efficacy and safety in 50 client-owned cats undergoing onychectomy and sterilization. Primary outcome parameters were analgesia score, gait/lameness score, and need for rescue analgesia assessed at times 0, 1, 4, 7, 24, 28, 35, 48, 52, 57 hours and on Day 5. Packed cell volume/total solids and serum biochemistry were assessed at time 0 and Days 3 and 5. There were no differences in efficacy and safety parameters regardless of the treatment protocol employed and no cat required rescue analgesia. The patients that received meloxicam preoperatively had statistically better gait/lameness scores than those that received meloxicam postoperatively, supporting the principle of preemptive analgesia.     

Ex vivo COX-1 and COX-2 inhibition in equine blood by phenylbutazone,flunixin meglumine,meloxicam and firocoxib: Informing clinical NSAID selection

Newer cyclo-oxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs), such as firocoxib, are proposed to reduce inhibition of cyclo-oxygenase-1 (COX-1) and avoid undesirable side effects, while continuing to inhibit inflammation associated with COX-2. However, COX selectivity is typically based on in vitro testing, which may not provide sufficient information critical for treatment selection. This study investigated the pharmacokinetics and ex vivo COX-1 and COX-2 inhibition of phenylbutazone, flunixin meglumine, meloxicam and firocoxib. Horses (n = 3) were administered one of the four drugs, in a randomised cross-over design, with 3-week washout periods. For each drug, three doses were given and sampling performed. Drug plasma concentrations, thromboxane B₂ (TXB₂) and prostaglandin E₂ (PGE₂) were determined. After one dose, TXB₂ and PGE₂ levels were significantly higher in horses administered firocoxib compared to flunixin meglumine. Following the third dose, TXB₂ levels in horses administered firocoxib and meloxicam were significantly higher compared to flunixin meglumine or phenylbutazone; all drugs reduced PGE₂ to a similar degree. The mean plasma half-lives were 5.97 ± 0.47, 4.74 ± 0.14, 8.24 ± 3.74 and 47.42 ± 7.41 h for phenylbutazone, flunixin meglumine, meloxicam and firocoxib, respectively. Firocoxib and meloxicam exhibited significantly less COX-1 inhibition compared to flunixin meglumine and phenylbutazone; all drugs inhibited COX-2. The plasma half-life of firocoxib was longer than the other NSAIDs, including meloxicam. Data from this study have important clinical relevance and should be used to inform practitioners’ drug selection of a COX-1 sparing or traditional NSAID and dose selection and to provide knowledge of the duration for the four NSAIDs studied.