氟尼辛葡甲胺对血液内毒素的影响

为研究氟尼辛葡甲胺对血液内毒素的影响,本实验选择预产期相近的长大母猪20头,随机分为实验组和对照组各10头。实验组母猪于分娩前15 d直至断奶,每1 000 kg日粮中添加1 kg高热血毒清(含10%氟尼辛葡甲胺),对照组不添加高热血毒清。采用鲎试验法检测内毒素、使用全自动生化分析仪测定肝功能、通过临床症状评估发病率。结果显示:实验组母猪和仔猪血液内毒素含量均极显著低于对照组(p0.01);实验组母猪便秘发生率、子宫内膜炎发生率、仔猪腹泻发生率和仔猪死亡率极显著低于对照组(p0.01);实验组母猪分娩前3 d至分娩后2 d的体温显著低于对照组(p0.05);实验组各日龄仔猪血清丙氨酸氨基转移酶和天门冬氨酸氨基转移酶均显著低于对照组(p0.05),γ-谷氨酰转移酶极显著低于对照组(p0.01)。本研究结果表明氟尼辛葡甲胺具有较强的抗内毒素作用,可以改善仔猪肝功能,为控制内毒素对猪的不良作用提供实验依据。     

Pressure algometry and thermal sensitivity for assessing pain sensitivity and effects of flunixin meglumine and sodium salicylate in a transient lameness model in sows

Sow lameness can result in decreased animal health and productivity, and is a significant animal welfare concern. Swine producers and veterinarians lack objective assessment tools to detect lameness. Objectives of this study were to evaluate pressure algometry (PA) and thermal sensitivity (TS) as objective assessment tools for changes in pain sensitivity associated with lameness and to assess analgesic drugs for mitigating lameness pain. Twelve mixed parity crossbred sows were anesthetized and injected with Amphotericin B in the distal interdigital space of both claws of one hind leg to induce transient lameness. Sows were randomly assigned to one of three analgesic treatment groups: (1) Sodium Salicylate (SS; 35 mg/kg per os q.12 h+0.04 ml/kg IM q.24 h sterile saline), (2) Flunixin meglumine (FM; 2.2 mg/kg IM q.24 h), or (3) Control (C; 0.04 ml/kg IM q.24 h sterile saline). All sows received each treatment over three trials with two-wk wash-out periods between trials. Forty-eight h post-induction, analgesic treatments were administered daily for four consecutive d. Pain sensitivity was assessed with PA and TS on each hind leg on d−1, d+1 and d+6 relative to induction (d0). Proc Glimmix of SAS 9.2 was used to analyze the difference between sound (S) and lame (L) legs on each trial day, with a simple effect comparison used to analyze effect of analgesia treatment on d+6. As predicted, S and L legs did not differ on d−1 (P=0.56) and less pressure was tolerated on L legs on d+1 (P<0.001) (Raw Means in kilograms of force: d−1 L 7.2±0.2; d−1 S 7.4±0.2; d+1 L 2.1±0.2; d+1 S 7.7±0.2 kgf). A simple effect comparison of d+6 revealed no differences between FM and C (p=0.90), FM and SS (p=0.17), or SS and C (p=0.07). The TS latency of S versus L legs differed on all trial days (d−1 p=0.02, d+1 p<0.0001, d+6 p<0.01) over all trials. (TS Raw means (s): d−1 L 7.3±0.6; d−1 S 9.1±0.6; d+1 L 3.3±0.2; d+1 S 6.8±0.6; d+6 L 6.0±0.6; d+6 S 8.4±0.7 s), including lame and sound days. In conclusion, these results support PA as an objective non-invasive method for measuring pain sensitivity in sows induced with transient lameness. Sodium salicylate or flunixin meglumine did not reduced pain sensitivity as measured by PA from d+1 to d+6 in this model of induced transient lameness.     

Pharmacokinetics of multiple doses of transdermal flunixin meglumine in adult Holstein dairy cows

A transdermal formulation of the nonsteroidal anti‐inflammatory drug, flunixin meglumine, has been approved in the United States and Canada for single‐dose administration. Transdermal flunixin meglumine was administered to 10 adult Holstein cows in their second or third lactation at the label dose of 3.33 mg/kg every 24 hr for three total treatments. Plasma flunixin concentrations were determined using high‐pressure liquid chromatography with mass spectroscopy (HPLC ‐MS ). Pharmacokinetic analysis was completed on each individual animal with noncompartmental methods using computer software. The time to maximum drug concentration (T max) was 2.81 hr, and the maximum drug concentration was 1.08 μg/ml. The mean terminal half‐life (T½) was determined to be 5.20 hr. Clearance per fraction absorbed (Cl/F) was calculated to be 0.294 L/hr kg^?1, and volume of distribution of fraction (V z/F ) absorbed was 2.20 L/kg. The mean accumulation factor was 1.10 after three doses. This indicates changes in dosing may not be required when giving multiple doses of flunixin transdermal. Further work is required to investigate the clinical efficacy of transdermal flunixin after multiple daily doses.     

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.     

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.     

Effect of the administration of flunixin meglumine on pregnancy rates in Holstein heifers

Fifty-two 15-month-old Holstein heifers were synchronised with single or double injections of prostaglandin F(2alpha), followed by an injection of gonadotrophin-releasing hormone (gnrh) 48 hours later, and inseminated 12 to 14 hours after the injection of gnrh (day 0). Half of them were then injected twice intramuscularly with 1.1 mg/kg flunixin meglumine 12 hours apart, on the evening of day 15 and the morning of day 16, and the other 26 were not treated. Pregnancy was diagnosed by ultrasound 29 and 65 days after they were inseminated. On day 29, 20 of the treated heifers were pregnant compared with 13 of the control heifers (P<0.05); on day 65, 18 of the treated heifers were still pregnant compared with 12 of the control heifers (P<0.10).     

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.     

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.     

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.     

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.     

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.     

Effectiveness of administration of phenylbutazone alone or concurrent administration of phenylbutazone and flunixin meglumine to alleviate lameness in horses

OBJECTIVE: To determine the effectiveness of administering multiple doses of phenylbutazone alone or a combination of phenylbutazone and flunixin meglumine to alleviate lameness in horses. ANIMALS: 29 adult horses with naturally occurring forelimb and hind limb lameness. PROCEDURES: Lameness evaluations were performed by use of kinematic evaluation while horses were trotting on a treadmill. Lameness evaluations were performed before and 12 hours after administration of 2 nonsteroidal anti-inflammatory drug (NSAID) treatment regimens. Phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days, or phenylbutazone paste was administered at approximately 2.2 mg/kg, PO, every 12 hours for 5 days in combination with flunixin meglumine administered at 1.1 mg/kg, IV, every 12 hours for 5 days. RESULTS: Alleviation of lameness was greater after administration of the combination of NSAIDs than after oral administration of phenylbutazone alone. Improvement in horses after a combination of NSAIDs did not completely mask lameness. Five horses did not improve after either NSAID treatment regimen. All posttreatment plasma concentrations of NSAIDs were less than those currently allowed by the United States Equestrian Federation Inc for a single NSAID. One horse administered the combination NSAID regimen died of acute necrotizing colitis during the study. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of a combination of NSAIDs at the dosages and intervals used in the study reported here alleviated the lameness condition more effectively than did oral administration of phenylbutazone alone. This may attract use of combinations of NSAIDs to increase performance despite potential toxic adverse effects.     

Effect of morphine and flunixin meglumine on isoflurane minimum alveolar concentration in goats

OBJECTIVE: To determine the effect of morphine and flunixin meglumine on isoflurane (ISO) minimum alveolar concentration (MAC) in goats. STUDY DESIGN: Prospective, randomized experimental study. ANIMALS: Five adult, wether goats from 1 to 3 years in age, and weighing 24-65 kg. METHODS: Anesthesia was induced using ISO, which was delivered via a mask. Goats were intubated and ventilated to maintain an end-tidal carbon dioxide concentration between 25 and 30 mm Hg (3.3-4 kPa). End-tidal ISO concentration was measured using an infrared analyzer. The baseline ISO MAC that prevented purposeful movement in response to clamping a claw was determined. Following baseline MAC determination, each goat received one of the following four treatments intravenously (IV): morphine (2 mg kg(-1)), flunixin (1.5 mg kg(-1)), flunixin (1.5 mg kg(-1)) plus morphine (2 mg kg(-1)) or saline, and the MAC was re-determined. Goats were studied at weekly intervals, and each goat received each treatment in a randomized fashion. RESULTS: The baseline ISO MAC for the control treatment was 1.43%. Morphine reduced the MAC by 29.7%. Flunixin did not significantly decrease the MAC nor did it potentiate the effect of morphine on MAC. The quality of recovery was good in all cases. CONCLUSIONS: Morphine (2 mg kg(-1), IV) significantly reduced the ISO MAC in goats and did not adversely affect the quality of recovery. CLINICAL RELEVANCE: The use of morphine, at the dose studied, in association with ISO anesthesia, will allow a clinically significant reduction in the concentration of ISO required to maintain general anesthesia in goats.     

Effect of lameness on the calving-to-conception interval in dairy cows

OBJECTIVE: To examine the relationship between lameness and the duration of the interval from calving to subsequent conception in lactating dairy cows. DESIGN: Cohort study. ANIMALS: 837 dairy cows. PROCEDURE: Cows affected with lameness were classified into 1 of 4 groups on the basis of types of disease or lesions observed, including foot rot, papillomatous digital dermatitis, claw lesions, or multiple lesions. Cows not affected with lameness were classified as healthy. Time from calving to conception was compared between lame cows and healthy cows. RESULTS: 254 (30%) cows were affected with lameness during lactation. Most lame cows (59%) had claw lesions. Lame cows with claw lesions were 0.52 times as likely to conceive as healthy cows. Median time to conception was 40 days longer in lame cows with claw lesions, compared with healthy cows. Number of breedings per conception for lame cows with claw lesions was significantly higher than that for healthy cows. CONCLUSION AND CLINICAL RELEVANCE: Claw lesions were the most important cause of lameness, impairing reproductive performance in dairy cows, as indicated by a higher incidence of affected cows and a greater time from calving to conception and a higher number of breedings required per conception, compared with healthy cows.     

Effect of wet weather on lameness in dairy cattle

The incidence of lameness in cows recorded by five veterinary practices over one year and one practice over four years was plotted with rainfall and potential soil moisture deficit. Correlation coefficients calculated between lameness, rainfall and potential soil moisture deficit over two-week periods showed the incidence of lameness in summer to be significantly related to the potential soil moisture deficit in the same two-week period and rainfall in the previous two-week period. Differences in patterns of lameness incidence among practices and years were also partly explained by differences in rainfall and potential soil moisture deficit; however, these effects were small compared with those of other factors that affect lameness incidence such as herd size, age and stage of lactation.     

Effect of lameness on milk yield in dairy cows

OBJECTIVE: To examine the relationship between lameness and milk yield in dairy cows. DESIGN: Cohort study. ANIMALS: 531 dairy cows. PROCEDURE: Cows affected with lameness were classified into 1 of 3 groups on the basis of type of diseases or lesions observed, including interdigital phlegmon (foot rot), papillomatous digital dermatitis (foot warts), or claw lesions. Cows not affected with lameness were classified as healthy. From Dairy Herd Improvement Association records, 305-day mature equivalent milk yield data were collected at the end of lactation or when the cow left the herd. Milk yield was compared between cows affected with lameness and healthy cows. RESULTS: 167 (31%) cows were affected with lameness during lactation. Lame cows had claw lesions (60%), papillomatous digital dermatitis (31%), or interdigital phlegmon (9%). Milk yield in lame cows with interdigital phlegmon (mean, 17,122 lb) was significantly less, compared with healthy cows (19,007 lb). CONCLUSIONS AND CLINICAL RELEVANCE: In this herd, interdigital phlegmon was associated with a 10% decrease in milk production. Lame cows with claw lesions or papillomatous digital dermatitis produced less milk than healthy cows, but the difference was not significant.