Post operative analgesic actions of flunixin in the cat

The post operative analgesic and sedative effects of flunixin (1 mgkg bwt) iv were investigated for the first 90 min post surgery in 20 cats undergoing a variety of surgical procedures. The results were compared with those obtained in another 20 cats, subjected to similar anaesthetic and surgical procedures, but treated with pethidine, 3 mgkg bwt iv. Post operatively, the analgesic effect of flunixin was shown to be adequate and its administration safe, so that it may reasonably be included among possible post operative analgesic treatments of choice in cats.     

Pharmacodynamics and pharmacokinetics of flunixin in the cat

The non-steroidal anti-inflammatory agent (NSAID) flunixin was administered as single doses both orally and intravenously to six cats at a dose rate of 1.0 mg/kg in a two-part cross-over study. After oral dosing rapid absorption to a mean peak concentration of 2.586 micrograms/ml occurred at a mean time of 1.33 h. Similar mean plasma concentration-time AUC values for oral and intravenous dosing indicated that absorption by the former route was virtually complete. The decline in plasma concentration occurred fairly rapidly with both routes, and elimination half-life was approximately 1.0-1.5 h. The time course of inhibition of serum TXB2 concentration was similar for the two routes of administration, suggesting that similar dosing schedules are likely to be appropriate for evaluation of flunixin in clinical trials.     

新兽药氟尼辛葡甲胺的解热镇痛作用

通过小鼠醋酸扭体法、家兔蛋白胨致热法对氟尼辛葡甲胺的解热、镇痛作用进行了研究。结果表明,氟尼辛葡甲胺具有明显的解热、镇痛作用。和对照组相比,氟尼辛葡甲胺4个剂量组（1.25、2.5、5、10 mg/kg）对醋酸所致的小鼠扭体反应均有极强的抑制作用,抑制率最高达100%。2.5 mg/kg的氟尼辛葡甲胺镇痛率即达82.7%,明显强于双氯芬酸钠（65.4%）和安乃近（58.7%）。对蛋白胨所致家兔发热的解热效果,氟尼辛葡甲胺高剂量组（4 mg/kg）优于安乃近组（0.2 g/kg）（P〈0.05）和氨基比林组（0.2 g/kg）（P〈0.01）。中剂量氟尼辛葡甲胺组（2 mg/kg）作用稍逊于安乃近组,但差异不显著。低剂量氟尼辛葡甲胺组（1 mg/kg）作用与氨基比林组相当。     

Pharmacokinetics of flunixin in the cat: enterohepatic circulation and active transport mechanism in the liver

The plasma and urine pharmacokinetics of flunixin-meglumine (FNX) in cats were examined using a total of 12 adult animals. After an intravenous injection of FNX (2 mg/kg), the plasma concentration time curves showed a profile of a two-compartment open model with an elimination half-life of 6.6 h. In spite of high plasma protein binding (>99%), the V(d)beta was unusually large, 0.7 L/kg. Although the recovery of FNX from urine was only 0.4% of the dose, the estimated inherent renal clearance closely corresponded to the renal plasma flow rate, indicating that a renal active tubular secretion was involved in the pharmacokinetics of FNX. Cholestyramine (ChSA), an anion exchanger, was orally administered immediately before the FNX injection in order to determine the involvement of enterohepatic circulation in FNX pharmacokinetics. The elimination phase of the profile of FNX was prevented by the concomitant administration of ChSA, so it was concluded that the drug undergoes enterohepatic circulation in cats. Pravastatin (PV) is a specific substrate of the type-2 organic anion transporting polypeptide transporter (OATP-2) in human liver cells. The effect of a concomitant intravenous injection of PV with FNX was examined in order to determine the involvement of OATP-2 like transporter in the pharmacokinetics. The V1 and total body clearance were decreased after the injection of PV. In conclusion, at least two active transport mechanisms are involved in the pharmacokinetics of FNX in cats. One pathway is renal tubular secretion and the other is sinusoidal active uptake by liver cells. The latter may be responsible for the enterohepatic circulation of FNX in cats.     

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)     

Pharmacokinetics of flunixin meglumine in the cow

Plasma levels of flunixin were measured in heifers after a single intravenous injection (1.1 mg kg-1), using high performance liquid chromatography. Plasma concentration versus time curves were best described by a two compartment model. The distribution phase (alpha) half-life was 0.294 hours, the elimination phase (beta) half-life was 8.12 hours and the volume of distribution was 1050 ml kg-1.     

Use of force plate analysis to compare the analgesic effects of intravenous administration of phenylbutazone and flunixin meglumine in horses with navicular syndrome

OBJECTIVE: To use force plate analysis to evaluate the analgesic efficacies of flunixin meglumine and phenylbutazone administered i.v. at typical clinical doses in horses with navicular syndrome. ANIMALS: 12 horses with navicular syndrome that were otherwise clinically normal. PROCEDURE: Horses received flunixin (1.1 mg/kg), phenylbutazone (4.4 mg/kg), or physiologic saline (0.9% NaCI; 1 mL/45 kg) solution administered IV once daily for 4 days with a 14-day washout period between treatments (3 treatments/horse). Before beginning treatment (baseline) and 6, 12, 24, and 30 hours after the fourth dose of each treatment, horses were evaluated by use of the American Association of Equine Practitioners lameness scoring system (half scores permitted) and peak vertical force of the forelimbs was measured via a force plate. RESULTS: At 6, 12, and 24 hours after the fourth treatment, subjective lameness evaluations and force plate data indicated significant improvement in lameness from baseline values in horses treated with flunixin or phenylbutazone, compared with control horses; at those time points, the assessed variables in flunixin- or phenylbutazone-treated horses were not significantly different. CONCLUSIONS AND CLINICAL RELEVANCE: In horses with navicular syndrome treated once daily for 4 days, typical clinical doses of flunixin and phenylbutazone resulted in similar significant improvement in lameness at 6, 12, and 24 hours after the final dose, compared with findings in horses treated with saline solution. The effect of flunixin or phenylbutazone was maintained for at least 24 hours. Flunixin meglumine and phenylbutazone appear to have similar analgesic effects in horses with navicular syndrome.     

Identification of flunixin glucuronide and depletion of flunixin and its marker residue in bovine milk

Residues of flunixin [and its marker residue 5‐hydroxyflunixin (5OHFLU)] were determined in milk from cows that intravenously received therapeutic doses of the drug. The samples were collected during each milking (every 12 h) for six consecutive days, and concentrations of flunixin and its metabolites were determined by the method with and without enzymatic hydrolysis (beta‐glucuronidase). The highest flunixin concentration in milk was observed 12 h after dosing (2.4 ± 1.42 μg/kg, mean ± SD). Flunixin concentrations in the samples determined with enzymatic hydrolysis were significantly higher (P < 0.05), which suggests the transfer of flunixin glucuronide to the milk. Additionally, unambiguous identification of flunixin glucuronide in the bovine milk was performed with linear ion‐trap mass spectrometry. The 5OHFLU concentrations analyzed without enzymatic hydrolysis (22.3 ± 16.04 μg/kg) were similar to this obtained with enzymatic hydrolysis. Flunixin and 5OHFLU concentrations dropped below the limits of detection at 48 h after last dosing.     

Pharmacokinetics of transdermal flunixin in sows

The objective of this study was to describe the pharmacokinetics (PK) of flunixin in 12 nonlactating sows following transdermal (TD) flunixin (3.33 mg/kg) and intravenous (IV; 2.20 mg/kg) flunixin meglumine (FM) administration using a crossover design with a 10‐day washout period. Blood samples were collected postadministration from sows receiving IV FM (3, 6, 10, 20, 40 min and 1, 3, 6, 12, 16, 24, 36, and 48 hr) and from sows receiving TD flunixin (10, 20, 40 min and 1, 2, 3, 4, 6, 8, 12, 16, 24, 36, 48, 60, and 72 hr). Liquid chromatography and mass spectrometry were used to determine plasma flunixin concentrations, and noncompartmental methods were used for PK analysis. The geometric mean ± SD area under the plasma concentration–time curve (AUC) following IV injection was 26,820.59 ± 9,033.88 and 511.83 ± 213.98 hr ng/ml for TD route. Mean initial plasma concentration (C₀) was 26,279.70 ± 3,610.00 ng/ml, and peak concentration (C_max) was 14.61 ± 7.85 ng/ml for IV and TD administration, respectively. The percent mean bioavailability of TD flunixin was 1.55 ± 1.00. Our results demonstrate that topical administration is not an efficient route for delivering flunixin in mature sows.     

Pharmacokinetics of flunixin meglumine in dogs

The pharmacokinetics of flunixin meglumine, a potent nonsteroidal anti-inflammatory agent, were studied in 6 intact, awake dogs. Plasma samples were obtained up to 12 hours after IV administration of flunixin meglumine. Flunixin concentration was determined, using high performance liquid chromatography. Plasma data best fit a 2-compartment model. Distribution half-life was 0.55 hour; elimination half-life was 3.7 hours; volume of distribution (area) was 0.35 L/kg; volume of distribution at steady state was 0.18 L/kg; volume of the central compartment was 0.079 L/kg; and total body clearance was 0.064 L/hr/kg. Flunixin concentrations obtained over a 6-hour period in 3 dogs with septic peritonitis did not differ significantly from those obtained from healthy dogs.     

The pharmacokinetics of flunixin meglumine in the sheep

Flunixin meglumine was administered intravenously and intramuscularly in sheep and the pharmacokinetics of the drug studied. Plasma concentrations of flunixin were measured by high performance liquid chromatography. The decline in plasma- flunixin concentration with time was best fitted by a triexponential equation. The pharmacokinetics following intravenous administration of 1.0 mg/kg indicate that flunixin has a rapid distribution half-life (t_½π= 2.3 min), a slow body clearance rate (Cl_b= 0.6 ml/kg/min) and an elimination half-life of 229 min. Similarly, at 2.0 mg/kg, flunixin is rapidly distributed from the plasma, t_½π= 2.7 min, has a slow body clearance rate (C/b = 0.7 mk/lg/min) and an elimination half-life of 205 min.
Following intramuscular injection flunixin is rapidly and well absorbed from the injection site. It had a mean maximum concentration ( C _max) of ≫5.9 μg/ml when administered at a dose rate of 1.1 mg/kg, and a relative bioavailability of 70%. Plasma concentrations increase proportionally to dose over the range 1.1 mg/kg-2.2 mg/kg when administered by the intramuscular route.     

Postoperative analgesic efficacy of meloxicam compared to tolfenamic acid in cats undergoing orthopaedic surgery

Objectives : To investigate the efficacy of meloxicam or tolfenamic acid administered preoperatively and postoperatively (five days in total) to cats undergoing surgical fracture repair. Methods : Eighty-eight otherwise healthy cats were matched according to fracture site and then randomly allocated to one of two groups, receiving 0·2 mg/kg meloxicam by subcutaneous injection (group M) or 1·5 to 3 mg/kg tolfenamic acid orally (group T) before anaesthesia. Analgesia was continued with 0.05 mg/kg oral meloxicam once daily or 1·5 to 3 mg/kg oral tolfenamic acid twice daily for four days postoperatively. Pain was assessed by a blinded observer using visual analogue scales and a functional limb score. The drug administrator assessed feed intake and palatability of the treatment. Results : Data from 66 cats were analysed. Visual analogue scale pain scores and functional limb scores decreased over time in both groups but were not significantly different between treatments. Feed intake was similar in both groups. Meloxicam was significantly more palatable than tolfenamic acid on all treatment days. Clinical Significance : Meloxicam and tolfenamic acid demonstrated comparable analgesia, without clinically observable side effects. Meloxicam may be associated with superior compliance in clinical practice due to the higher palatability and once daily treatment resulting in better ease of administration.     

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.     

Endotoxin-induced bovine mastitis: immunoglobulins, phagocytosis, and effect of flunixin meglumine

Milk whey immunoglobulins (Ig) and phagocytosis of staphylococci by milk polymorphonuclear neutrophilic leukocytes (PMN) were measured in 12 cows (allotted to 6 pairs) during acute bovine mastitis induced by intramammary inoculation of endotoxin. Six of these cows (or 1 in each pair) were treated with flunixin meglumine and were compared with the others (given only saline solution). The endotoxin inoculation comprised 10 micrograms of Escherichia coli O26:B6 lipopolysaccharide injected into one of the rear quarters (mammae). Flunixin meglumine was administered parenterally at a dosage of 1.1 mg/kg every 8 hours (total of 7 doses) beginning at 2 hours after endotoxin was injected. Milk samples were obtained, and whey samples were prepared from each quarter of each cow 3 times before inoculation and at 2, 4, 8, 12, 24, 48, 72, 96, 120, 144, 168, and 336 hours after endotoxin was inoculated. Significant increases (P less than 0.05) in milk whey IgG1, IgG2, IgM, and IgA concentrations were observed in whey samples from endotoxin-inoculated quarters. Greatest relative increase was seen for IgG2. Increased whey Ig concentrations were not observed in quarters which were not inoculated with endotoxin. Concentrations of whey IgG1 and IgM in endotoxin-inoculated quarters were significantly (P less than 0.05) decreased in flunixin meglumine-treated cows, compared with those in saline solution-treated cows. Significant increases in phagocytosis of staphylococci by milk PMN were observed in whey samples from endotoxin-inoculated quarters. Significant differences in PMN phagocytosis were not found in whey samples from cows given flunixin meglumine when compared with whey samples from cows given saline solution.     

氟尼辛葡甲胺对猪实验性链球菌感染的解热作用

氟尼辛(flunxin),是美国先灵葆雅公司于20世纪90年代开发的兽用非甾体类抗炎药,主要通过抑制环氧化酶、减少前列腺素等炎性介质的生成而发挥解热、抗炎和镇痛作用[1].