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.     

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.     

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.     

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.     

Clinical efficacy of meloxicam (Metacam) and flunixin (Finadyne) as adjuncts to antibacterial treatment of respiratory disease in fattening cattle

The clinical efficacy of two non-steroidal anti-inflammatory drugs (NSAIDs), meloxicam (Metacam 20 mg/ml) and flunixin meglumine (Finadyne), as adjuncts to antibacterial therapy in the treatment of acute febrile respiratory disease in cattle was compared. The randomised blind, positive controlled study was conducted under feedlot conditions in Mexico. Overall, 201 female cattle (weighing 220-250 kg) diagnosed with bronchopneumonia at the feedlot were recruited into the study. On Day 0 all animals were treated with 20 mg oxytetracycline/kg body-weight (Bivatop 200) by subcutaneous injection, in conjunction with either meloxicam (0.5 mg/kg subcutaneously, Metacam 20 mg/ml, n = 100), or flunixin meglumine (2.2 mg/kg intravenously, Finadyne, n = 101). According to label instructions, meloxicam was administered as a single dose, whereas flunixin meglumine could be administered daily for up to 3 consecutive days depending on the rectal temperature (with re-administration, if rectal temperature > or = 40.0 degrees C). Rectal temperature, respiratory rate, appetite, dyspnoea, coughing, nasal discharge and general condition were recorded on Days 0 (prior to treatment), 1, 2, 3 and 7 using a weighted numerical score. Scores were summed to generate a 'Clinical Sum Score' (CSS, range 7 to 24 points). Individual animal body weights were measured on Days 0 and 7. Nasal swabs were collected from 10 animals per treatment group on Day 0 for microbiological culture. Clinical parameters and the mean CSS showed no significant differences between treatment groups with mean CSS on Days 0 and 7 of 16.18 and 10.55 in the meloxicam group and 16.41 and 10.88 in the flunixin meglumine group. However, a significantly lower mean rectal temperature was measured in the meloxicam group on Day 2 (p < or = 0.01). No significant differences in mean body weights were found between groups. Repeated administration of flunixin meglumine was performed in 45% of the animals. No suspected adverse drug events related to treatments were reported. It is concluded that a single subcutaneous dose of meloxicam was as clinically effective as up to 3 consecutive daily intravenous doses of flunixin meglumine when used as an adjunctive therapy to antibacterial therapy in the treatment of acute febrile respiratory disease in feedlot cattle.     

Effect of flunixin meglumine on Escherichia coli heat-stable enterotoxin-induced diarrhea in calves

In a study to evaluate the effect of flunixin meglumine on secretory diarrhea, 11 calves were assigned to 3 groups: group 1 (n = 3) served as controls, group-2 calves (n = 4) were given 2.2 mg of flunixin meglumine/kg, IM at 7 AM and 3 PM, and group-3 calves (n = 4) were given 2.2 mg of flunixin meglumine/kg, IM at 7 AM, 11 AM, and 3 PM. All calves were given approximately 200 micrograms of heat-stable Escherichia coli enterotoxin (STa) orally at 8 AM. Mean cumulative fecal output for groups 1, 2, and 3 was 1,331.0 +/- 317.2 g, 1,544.3 +/- 154.4 g, and 785.5 +/- 276.5 g, respectively. There was a significant (P less than 0.05) reduction in mean fecal output in group-3 calves, compared with that in groups 1 and 2. Calves in group 2 tended to have a delay, but not a reduction, in their fecal output. At 12 hours, hemoconcentration was significantly (P less than 0.05) greater in group-1 calves than in group-2 or group-3 calves.     

Hemodynamics, plasma eicosanoid concentrations, and plasma biochemical changes in calves given multiple injections of Escherichia coli endotoxin

Twelve male neonatal calves (39 to 50 kg) were allotted to 3 groups of 4 calves each. All calves were anesthetized with halothane, and then Escherichia coli endotoxin was given intravenously (3 times) and intraperitoneally (3 times) during a 6-hour period. Group-1 calves were untreated, group-2 calves were pretreated with a low dose of flunixin meglumine (1.1 mg/kg of body weight), and group-3 calves were pretreated with a high dose of flunixin meglumine (4.4 mg/kg). In calves of group 1, the mean systemic arterial blood pressure (MABP) and cardiac output (CO) decreased, but pulmonary arterial pressure increased after the initial intravenous and intraperitoneal injections of endotoxin. In calves of this group, these changes were accompanied by increased plasma thromboxane B2 (TxB2) concentration. During this period, increased plasma TxB2 concentration or hemodynamic changes were not detected in calves of groups 2 and 3. Only calves of group 1 had altered hemodynamics early in the experiment; however, after 6 hours, calves of all 3 groups had similarly decreased CO and MABP. In calves of the untreated group, plasma 6-keto-prostaglandin (PG)F1 alpha concentration increased steadily from the beginning of the experiment until 3 hours later. The CO and MABP were low at the time when serum 6-keto-PGF1 alpha concentration was high; however, these 2 measurements also were low in treated calves who did not have correspondingly high plasma 6-keto-PGF1 alpha concentration. Regional blood flow analysis did not reveal correlations between prostanoid concentrations and altered blood flow to selected tissues.(ABSTRACT TRUNCATED AT 250 WORDS)     

Netobimin in drinking water for treatment of bovine parasitic bronchitis: a field experiment

Lungworm-infected seeder calves were used on four 1.41 ha paddocks to ensure that groups of 11 calves would be exposed to a heavy challenge with Dictyocaulus viviparus. By the 39th day after turnout there was a serious episode of respiratory disease and a diagnosis of parasitic bronchitis was confirmed by post mortem and faecal examination. One group of trial calves was treated with netobimin administered in the drinking water at 2.8 mg/kg/day for seven consecutive days; another group received the same treatment supplemented with flunixin meglumine at 2.2 mg/kg/day for three days; a third group was given a single oral dose of 7.5 mg netobimin/kg; only emergency treatments were given to calves in the control group. The clinical response to the drinking water treatments was highly satisfactory and better than the response to the single oral treatment.     

Comparative therapeutic effect of steroidal and non-steroidal anti-inflammatory drugs on pro-inflammatory cytokine production in water buffalo calves (<Emphasis Type="Italic">Bubalus bubalis</Emphasis>) naturally infected with bronchopneumonia: a randomized clinical trial

In the current study, we compared the therapeutic effects of a non-steroidal and a steroidal anti-inflammatory drug on the production of pro-inflammatory cytokines, interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-12p40 (IL-12p40), interferon gamma (IFNγ), and tumor necrosis factor alpha (TNF-α) in the blood of water buffalo (Bubalus bubalis) calves naturally infected by bronchopneumonia. Twenty-seven buffalo calves (7 ± 2-month-old, 163 ± 12 kg) reared in smallholder farms in El-Dakahlia province in Egypt were identified to have bronchopneumonia and randomly allocated into three equal groups. Ten clinically healthy buffalo calves with negative bronchoalveolar lavage results were served as negative control. Diseased calves were treated with tulathromycin alone, a combination of tulathromycin with dexamethasone (steroidal anti-inflammatory drug) or tulathromycin with flunixin meglumine (non-steroidal anti-inflammatory drug). The results revealed significant elevations (P < 0.05) in the production of selected cytokines in all diseased calves in comparison with healthy animals. Six days post-treatment, a significant inhibition (P < 0.05) in the production of all assessed cytokines was observed in the blood of all treated calves. Interestingly, the serum concentrations of IL-1β and IL-12p40 were returned to the normal levels in pneumonic calves treated with the combination therapy of tulathromycin and flunixin meglumine. A strong significant positive correlation (P < 0.05) was detected between clinical sum scoring and IL-12p40 and TNF-α concentrations. The obtained results indicate the selectively potent anti-inflammatory effect of flunixin meglumine on the production of pro-inflammatory cytokines in pneumonic buffalo calves and highlight the efficacy of flunixin meglumine in the treatment of bronchopneumonia in buffalo calves when used in combination with tulathromycin.     

The efficacy of dexamethasone and flunixin meglumine in treating endotoxin-induced changes in calves

Eicosanoids have been implicated in the pathophysiology of endotoxic shock. Drugs which alter eicosanoid production such as corticosteroids and non-steroidal anti-inflammatory drugs (NSAID) are beneficial in treating endotoxic shock. Experiments were conducted to investigate the efficacy of dexamethasone, a corticosteroid, and/or flunixin meglumine, a NSAID, in treating endotoxin-induced changes in calves.Fourteen male calves were assigned to one of four treatment groups: group 1, endotoxin-untreated; group 2, endotoxin-flunixin meglumine treated; group 3, endotoxin-dexamethasone-treated; group 4, endotoxin-flunixin meglumine and dexamethasone-treated. Each calf was given three intravenous and intraperitoneal injections of E. coli endotoxin. Hemodynamic, blood gas, blood chemical and eicosanoid level determinations were obtained.Thirty minutes after endotoxin injection, pulmonary artery pressure (PAP) increased and cardiac output (CO) decreased compared with baseline, corresponding to increased thromboxaneB₂ levels in groups 1 and 3. These groups exhibited a decreased mean arterial pressure (MAP) at three and five hours corresponding to increased 6-keto-prostaglandinF_lalpha. The MAP, PAP and CO of group 4 remained near baseline for the entire six hours, except for a late drop in MAP. Lactic acid levels were significantly increased and arterial bicarbonate levels were reduced by six hours in all groups except for group 4. These results indicate that the combination treatment of flunixin meglumine and dexamethasone prevents many of the metabolic derangements observed during endotoxic shock in calves.     

Attenuation of ischaemic injury in the equine jejunum by administration of systemic lidocaine

REASONS FOR PERFORMING STUDY: Absorption of endotoxin across ischaemic-injured mucosa is a major cause of mortality after colic surgery. Recent studies have shown that flunixin meglumine retards mucosal repair. Systemic lidocaine has been used to treat post operative ileus, but it also has novel anti-inflammatory effects that could improve mucosal recovery after ischaemic injury. HYPOTHESIS: Systemic lidocaine ameliorates the deleterious negative effects of flunixin meglumine on recovery of mucosal barrier function. METHODS: Horses were treated i.v. immediately before anaesthesia with either 0.9% saline 1 ml/50 kg bwt, flunixin meglumine 1 mg/kg bwt every 12 h or lidocaine 1.3 mg/kg bwt loading dose followed by 0.05 mg/kg bwt/min constant rate infusion, or both flunixin meglumine and lidocaine, with 6 horses allocated randomly to each group. Two sections of jejunum were subjected to 2 h of ischaemia by temporary occlusion of the local blood supply, via a midline celiotomy. Horses were monitored with a behavioural pain score and were subjected to euthanasia 18 h after reversal of ischaemia. Ischaemic-injured and control jejunum was mounted in Ussing chambers for measurement of transepithelial electrical resistance (TER) and permeability to lipopolysaccharide (LPS). RESULTS: In ischaemic-injured jejunum TER was significantly higher in horses treated with saline, lidocaine or lidocaine and flunixin meglumine combined, compared to horses treated with flunixin meglumine. In ischaemic-injured jejunum LPS permeability was significantly increased in horses treated with flunixin meglumine alone. Behavioural pain scores did not increase significantly after surgery in horses treated with flunixin meglumine. CONCLUSIONS: Treatment with systemic lidocaine ameliorated the inhibitory effects of flunixin meglumine on recovery of the mucosal barrier from ischaemic injury, when the 2 treatments were combined. The mechanism of lidocaine in improving mucosal repair has not yet been elucidated.     

Effects of flunixin meglumine in dogs following experimentally induced endotoxemia

Twelve dogs were randomly divided into three groups. Group 1 dogs were given Escherichia coli endotoxin and then treated with flunixin meglumine. Group 2 dogs were given endotoxin as group 1, but untreated. Group 3 dogs were given flunixin meglumine alone. The dogs were monitored clinically and urine and serum samples were collected at regular intervals for 72 hours. All surviving dogs were humanely killed after 72 hours and examined for gross and histologic lesions. Group 1 dogs all survived 72 hours, but showed prerenal azotemia, hepatocellular damage, hemorrhagic enteritis, and numerous gastric ulcerations. Three of the four dogs in group 2 died before 72 hours. Group 2 dogs showed many of the same chemical and hemodynamic changes as group 1. They had severe hemorrhage into the intestinal lumen; however, there were no gastric ulcerations. Group 3 dogs all survived and showed little physical or hematologic change. The study suggested the following: 1) flunixin meglumine was an effective drug in ameliorating the fatal effects of canine endotoxemia, 2) the effects of endotoxin in combination with flunixin meglumine, at 1.1 mg/kg body weight, caused gastric ulcerations, and 3) in normal dogs flunixin meglumine at 1.1 mg/kg body weight did not cause severe side effects or gross lesions.     

Effects of flunixin and flunixin plus prednisone on the gastrointestinal tract of dogs

Flunixin meglumine has been reported to induce gastrointestinal lesions in dogs when administered at therapeutic dosages. We administered flunixin meglumine to dogs daily for 10 days to assess the effect of this drug on the gastrointestinal tract. We also evaluated the possibility of corticosteroid potentiation of gastrointestinal toxicosis by concurrent administration of prednisone to 1 group of dogs. Dogs were monitored for gastrointestinal toxicosis by means of serial endoscopic evaluation, measurement of fecal occult blood, PCV, and total solid concentration, and by physical examination. There were 3 treatment groups of 5 dogs each. Group-1 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM; group-2 dogs were given 4.4 mg of flunixin meglumine/kg daily, in 2 divided doses IM; and group-3 dogs were given 2.2 mg of flunixin meglumine/kg daily, in 2 divided doses IM plus 1.1 mg of prednisone/kg/d orally, in 2 divided doses. A fourth group of 5 dogs served as a control group. Endoscopically visible gastric mucosal lesions developed in all treated dogs within 4 days of initiating treatment. Lesions first developed in the gastric pylorus and antrum and lesions at these sites were more severe than those observed elsewhere. Dogs treated with flunixin meglumine plus prednisone developed the earliest and most severe lesions; lesion scores in group-2 dogs were higher than those in group-1 dogs. All dogs treated had occult blood in their feces by day 5 and its presence appeared to correlate more closely with endoscopic findings than did physical examination findings or changes in values for PCV or total solids.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic flunixin meglumine therapy in foals

Effects of a therapeutic dose of flunixin meglumine on gastric mucosa of horse foals were determined by endoscopy, double-contrast radiography, and gross and histologic examinations. Foals were administered 1.1 mg of flunixin meglumine/kg of body weight, PO/day for 30 days in an encapsulated form that was divided into 2 doses/day (group 1; n = 3) or by IM injection once a day (group 2; n = 7). Three control foals (group 3; n = 3) were administered capsules (n = 1) containing dextrose powder or IM injections (n = 2) of vehicle solution without flunixin meglumine. All 3 groups-1 foals given flunixin meglumine PO developed oral ulcers. Group-2 foals given flunixin meglumine IM did not develop oral ulcers. One control foal (group 3) developed 1 oral ulcer that healed during the study. Endoscopic examination revealed linear crease-like mucosal lesions in the glandular portion of the stomach in 2 group-2 foals. Radiographic evidence of gastric ulcers was observed in only 1 gastrogram of a group-1 foal. Foals were euthanatized, and necropsy revealed erosions and/or ulcers of the glandular portion of the stomach. Oral ulcers were observed in all 3 group-1 foals. Erosions of the glandular portion of the stomach developed in all 10 foals given flunixin meglumine, but did not develop in group-3 foals. Ulceration of the glandular portion of the stomach was present in 1 group-2 foal.     

Flunixin meglumine and flurbiprofen in cows with experimental Escherichia coli mastitis

The effect of flunixin meglumine and flurbiprofen on the course of experimental Escherichia coli mastitis was examined. Nine cows (within one month post partum) were inoculated intramammarily with 20 x 10(5) viable E coli in both rear quarters. Three cows remained untreated (controls); three cows received three injections of flunixin meglumine and three cows received flurbiprofen as two intravenous infusions. Flunixin meglumine and flurbiprofen were initially given before clinical signs were observed. Treatment was repeated if the cows' temperature increased by more than 1 degree C. In the untreated cows, rectal temperature and heart rate increased from three hours after infection, and rumen motility (both frequency and amplitude) decreased from four hours after infection. Treatment with flunixin meglumine or flurbiprofen almost completely abolished the febrile response during the first nine hours after infection, and the decrease in rumen motility was less pronounced in the treated animals. These results suggest that the decrease in rumen motility during E coli mastitis is at least partly due to a mechanism involving prostaglandin.     

Effect of age and training status on pharmacokinetics of flunixin meglumine in thoroughbreds

The effect of age and training status on the pharmacokinetics of flunixin meglumine was evaluated in 16 Thoroughbreds. Horses were assigned to 1 of 3 groups on the basis of age and training status: group A (n = 6), horses in active training and less than or equal to 5 years old; group B (n = 5), horses out of training for a minimum of 6 weeks and less than or equal to 5 years old; and group C (n = 5), horses out of training for at least 2 years and greater than or equal to 9 years old. After administration of 500 mg of flunixin meglumine IV, multiple serum and urine samples were obtained over 24 hours and assayed for flunixin by high-performance liquid chromatography. Although the mean distribution rate constant and volume of distribution were similar for the 3 groups, mean total body clearance and elimination rate constant were significantly (P less than 0.05) greater and half-life significantly (P less than 0.01) less in groups A and B, compared with group C. Differences in pharmacokinetic values were not observed between the horses in group A and B. In addition, the changes in clearance, elimination rate constant, and half-life of flunixin were found to significantly (P less than 0.05) correlate with age. The results of this investigation indicated that age, but not training status, influences disposition of flunixin meglumine in Thoroughbreds.     

Effect of flunixin meglumine on surgical wound strength and healing in the rat

Forty male adolescent Sprague-Dawley rats were anesthetized and standardized ventral midline laparotomies and uniform-length gastrotomies and typhlotomies were performed. The visceral and abdominal surgically inflicted wounds were closed with 5-0 polypropylene and 4-0 nylon suture, respectively. The rats were allotted into 4 groups (10 rats/group); 2 groups were not given flunixin meglumine (controls) and 2 groups were given flunixin meglumine (1.1 mg/kg of body weight, IM, every 12 hours). On day 5 and again on day 14 after surgery, 1 control and 1 flunixin meglumine-treated group were euthanatized. Tensile strength of the skin and linea alba incisions was determined, using a computerized tensiometer. Gastric and cecal incision bursting strengths were determined, using a pressure manometer. Flunixin meglumine significantly (P less than 0.05) decreased the tensile strength of wounds in the skin and linea alba, but did not affect visceral bursting strength at day 5 after surgery. At day 14 after surgery, a significant difference in wound strength was not found between the flunixin meglumine and control groups in any of the tissues evaluated. Flunixin meglumine had an adverse influence on the inflammatory stage of wound repair, but not on the proliferative stage, when fibroplasia is a major factor in wound strength. Major histologic differences were not found in the incision wounds of flunixin meglumine-treated and nontreated control rats.     

Effect of flunixin meglumine on cytokine levels in experimental endotoxemia in mice

In this study, effect of flunixin meglumine on serum tumour necrosis factor alpha, (TNFalpha) interleukin-1 beta and interleukin-10 levels was investigated in lipopolysaccharide-induced endotoxic mice. Healthy 273 Balb/C mice were used and divided into three equal groups. Group 1 was injected lipopolysaccharide (Escherichia coli 0111:B4, 250 microg/mouse, intraperitoneally), Group 2 was injected flunixin meglumine (2.5 mg/kg, subcutaneously), and Group 3 was injected lipopolysaccharide + flunixin meglumine. After the treatments, at 0., 1., 2., 3., 6., 12., 24th hours and 3., 5., 7., 14., 21., 28th days blood samples were taken from seven mice in each group. Serum TNFalpha, interleukin-1 beta and interleukin-10 levels were measured using commercially available kits by enzyme-linked immunoassay. Flunixin meglumine did not affect the cytokine levels in healthy animals. While lipopolysaccharide increased serum TNFalpha, interleukin-1 beta and interleukin-10 levels, flunixin meglumine inhibited increases at levels of all cytokines. As result, flunixin meglumine showed depressor effect on cytokine levels in endotoxemia and the effect may be a reason for the first chosen member of nonsteroid anti-inflammatory drug in endotoxemia.     

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.     

Clinical and pathological effects of flunixin meglumine administration to neonatal foals.

The effects of daily intravenous administration of flunixin meglumine at dosages of 0.55, 1.1, 2.2 and 6.6 mg/kg for five days were examined in neonatal foals. Six two day old foals were used to evaluate the effect of each dosage. Foals were examined every day and blood samples collected on days 1, 3 and 6. All foals were euthanized after six days, necropsied and examined for lesions. The major clinical abnormality was diarrhea, but the incidence was not related to the dosage of flunixin meglumine administered. The foals receiving 6.6 mg/kg of flunixin meglumine had significantly more gastrointestinal ulceration and greater cecal pathology and cecal petechiation scores than those foals treated with saline. The foals in the 6.6 mg/kg treatment group had a greater loss of total protein during the study, but the difference was not significant. There were no statistically significant blood cellular or biochemical alterations associated with the administration of flunixin meglumine. There were no significant clinicopathological differences between healthy foals treated with the recommended dosage of flunixin meglumine and those treated with physiological saline.