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Abstract Two solid-contact electrochemical sensors were developed for detection of each of oxytetracycline HCl (OXY), and the co-formulated non-steroidal anti-inflammatory drug flunixin meglumine (FLU) in veterinary formulations and animal-derived food products. The designed sensors were based on a glassy carbon electrode as the substrate material and high molecular weight polyvinyl chloride (PVC) polymeric ion-sensing membranes doped with multiwalled carbon nanotubes (MWCNTs) to improve the potential stability and minimize signal drift. For determination of OXY, the sensing membrane was modified with potassium tetrakis (4-chlorophenyl) borate (K-TCPB), which was employed as a cation exchanger, and 2-hydroxypropyl-β-cyclodextrin (HP-ßCD), which was used as an ionophore. A linear response within a concentration range of 1 × 10− 6-1 × 10− 2 M with a slope of 59.47 mV/decade over a pH range of 1–5 was recorded. For the first time, two potentiometric electrodes were developed for determination of FLU, where the sensing membrane was modified with tetra dodecyl ammonium chloride (TDDAC) as an anion exchanger. A linear response within a concentration range of 1 × 10− 5-1 × 10− 2 M and a slope of -58.21 mV/decade over a pH range of 6–11 was observed. The suggested sensors were utilized for the selective determination of each drug in pure powder form, in veterinary formulations, and in spiked milk samples, with mean recoveries ranging from 98.50 to 102.10, and without any observed interference. The results acquired by the proposed sensors were statistically analyzed and compared with those acquired by the official methods, and the results showed no significant difference. Graphical Abstract

ABSTRACT This study aimed to compare the inhibitory effect of flunixin meglumine and meloxicam on the smooth muscles of the gastrointestinal tract in male cattle. Tissue samples, including the abomasum, ileum, proximal loop and centripetal gyri of the ascending colon, were collected from routinely slaughtered male cattle. These samples were sectioned into strips and mounted in an isolated tissue bath system. Smooth muscle contractions were evoked using carbachol, and cumulative doses of atropine, flunixin meglumine and meloxicam were administered to assess smooth muscle activity. Atropine, used as a positive control, did not abolish contractions in the abomasum and centripetal gyri tissues, even at a high concentration of 10 µM. Based on area‐under‐curve values, flunixin meglumine demonstrated a greater inhibitory effect than meloxicam by factors of 8.57, 4.28, 12.44 and 3.93 in the abomasum, ileum, proximal loop and centripetal gyri tissues, respectively. For beats‐per‐minute values, flunixin meglumine exhibited a stronger inhibitory effect than meloxicam by factors of 7.22, 3.88, 7.03 and 3.35 in the abomasum, ileum, proximal loop and centripetal gyri tissues, respectively. Finally, based on peak maximum values, flunixin meglumine's inhibitory effect was 6.13, 4.43, 7.07 and 7.02 times greater than that of meloxicam in the abomasum, ileum, proximal loop and centripetal gyri tissues, respectively. In conclusion, flunixin meglumine was more potent than meloxicam in inhibiting smooth muscle activity. Conversely, meloxicam is associated with fewer adverse effects due to its selective action on the cyclooxygenase‐2 enzyme. However, flunixin meglumine may be more advantageous than meloxicam for applications in beef and milk production due to its shorter residue elimination time.

Lipopolysaccharide (LPS), known as a stimulant of inflammation, causes acute liver injury by inducing the production of inflammatory mediators and oxidative stress. The purpose of this study is to determine whether of a nonsteroidal anti–inflammatory drug (NSAID) Flunixin meglumine (FM) and herbal an medicine Ginkgo biloba L. extract (GBE) show antioxidative, anti–inflammatory or antiapoptotic effects in liver tissue in LPS–induced hepatotoxicity. Animals were separated to 6 groups as control, sepsis (1 mg·kg-1, 7th day single dose, intraperitoneal (ip)), sepsis + FM (1 mg·kg-1, 7th day single dose, ip + 2.2 mg·kg-1 day, ip), sepsis + GBE (1 mg·kg-1, 7th day single dose, ip + 50 mg·kg-1 day, gavage), FM and GBE and the study continued for 7 days. Liver tissues taken from rats sacrificed were analyzed biochemically, histologically and immunohistochemically. Accordingly, LPS caused liver function markers alteration, inflammation, oxidative stress, and apoptosis, as well as histopathological changes in liver tissue. However, it was observed that LPS–induced changes were regulated by FM and GBE application. FM and GBE was demonstrated to have antioxidant, antiinflammatory and anti–apoptotic properties in LPS–induced hepatotoxicity.

Advanced age, called geriatrics, negatively affects the aging–related physiological changes on bodysystems. non–steroidal anti–inflammatory drugs (NSAIDs) used in geriatric pets or humans have negative effects on the kidneys. For this purpose, , the effects of Meloxicam and Flunixin Meglumine, which are NSAIDs frequently used in Veterinary Medicine, on the liver and kidney structure and function in geriatric male rats were evaluated. Twenty–four male geriatric rats (30–36 month old) and twenty–four 3–month–old young male Wistar albino rats were used in the study. Six groups were created, with eight rats in each group: young control (YC), young Meloxicam (YM), young Flunixin Meglubine (YFM), geriatric control (GC), geriatric meloxicam (GM), geriatric Flunixin Meglubine (GFM). Control groups (YC and GC) received an intraperitoneal injection of saline using the same volume as in the othergroups. Meloxicam was administered at 5.8 mg·kg-1 to the YM and GM groups, and Flunixin Meglumine at 2.5 mg·kg-1 intraperitoneally to the YFM and GFM groups once a day for 5 days. Neutrophil Gelatinase–Associated Lipocalin (NGAL), Cystatin C (Cyc–c), Kidney Injury Molecule–1 (KIM–1), Interleukin–18 (IL–18), Urea, Creatinine (Crea), Albumin (Alb), and Total Protein (TP) levels, were determined in sera and urine samples. Serum NGAL, Cys–C, and KIM–1 levels in the GC group were found to be significantly higher than those in the YC group (P

This study aims to report the treatment of retained placenta in a doe by administration of intrauterine antibiotics, accompanied by intramuscular injection of antibiotics, anti-inflammatory, and injection of vitamins A, D, and E as supportive treatment. The Saanen doe was brown, approximately two years old with a BCS of 3/5 and kidding for the first time on January 11, 2023. The following day, it was reported that the doe's placenta had not been expelled until 24 hours after kidding. Physically the doe was weak, unable to stand, and reddish-brown discharge was seen came out of the vulva. Based on these conditions the doe was diagnosed as having retained placenta with a fausta prognosis. The doe was treated with a bolus of antibiotics contained 250 mg sulphadiazine and 50 mg trimethoprim which was diluted with 5 mL of 0.9% NaCl for uterine lavage. Systemic treatment consisted of intramuscular injection of ceftiofur at 1.1 mg/kg bw, flunixin meglumine at 1.1 mg/kg bw, as well as a combination of 300,000 IU of vitamin A palmitate, 100,000 IU of vitamin D3, and 50 mg of vitamin E acetate as supportive treatment. The treatment was successful, the doe was able to stand and eat when examined the next day after treatment. The doe returned to estrus 42 days after treatment. It could be concluded that treatment of retained placenta in a doe with intrauterine broad-spectrum antibiotics, beta-lactamase antibiotics and intramuscular anti-inflammatory, with vitamins A, D and E as supportive therapy was effective and the doe returned to estrus 42 days after treatment.

This study aims to report the treatment of retained placenta in a doe by administration of intrauterine antibiotics, accompanied by intramuscular injection of antibiotics, anti-inflammatory, and injection of vitamins A, D, and E as supportive treatment. The Saanen doe was brown, approximately two years old with a BCS of 3/5 and kidding for the first time on January 11, 2023. The following day, it was reported that the doe's placenta had not been expelled until 24 hours after kidding. Physically the doe was weak, unable to stand, and reddish-brown discharge was seen came out of the vulva. Based on these conditions the doe was diagnosed as having retained placenta with a fausta prognosis. The doe was treated with a bolus of antibiotics contained 250 mg sulphadiazine and 50 mg trimethoprim which was diluted with 5 mL of 0.9% NaCl for uterine lavage. Systemic treatment consisted of intramuscular injection of ceftiofur at 1.1 mg/kg bw, flunixin meglumine at 1.1 mg/kg bw, as well as a combination of 300,000 IU of vitamin A palmitate, 100,000 IU of vitamin D3, and 50 mg of vitamin E acetate as supportive treatment. The treatment was successful, the doe was able to stand and eat when examined the next day after treatment. The doe returned to estrus 42 days after treatment. It could be concluded that treatment of retained placenta in a doe with intrauterine broad-spectrum antibiotics, beta-lactamase antibiotics and intramuscular antiinflammatory, with vitamins A, D and E as supportive therapy was effective and the doe returned to estrus 42 days after treatment. [ABSTRACT FROM AUTHOR]

ABSTRACT: Excessive and protracted lipolysis in adipose tissues of dairy cows is a major risk factor for clinical ketosis (CK). This metabolic disease is common in postpartum cows when lipolysis provides fatty acids as an energy substrate to offset negative energy balance. Lipolysis in cows can be induced by the canonical (hormonally induced) and inflammatory pathways. Current treatments for CK focus on improving glucose in blood (i.e., oral propylene glycol [PG], or i.v. dextrose). However, these therapies do not inhibit the canonical and inflammatory lipolytic pathways. Niacin (NIA) can reduce activation of the canonical pathway. Blocking inflammatory responses with cyclooxygenase inhibitors such as flunixin meglumine (FM) can inhibit inflammatory lipolytic activity. The objective of this study was to determine the effects of including NIA and FM in the standard PG treatment for postpartum CK on circulating concentrations of ketone bodies. A 4-group, parallel, individually randomized trial was conducted in multiparous Jersey cows (n = 80) from a commercial dairy in Michigan during a 7-mo period. Eligible cows had CK symptoms (lethargy, depressed appetite, and milk yield) and hyperketonemia (blood β-hydroxybutyrate [BHB] ≥1.2 mmol/L). Cows with CK were randomly assigned to 1 of 3 groups where the first group received 310 g of oral PG once per day for 5 d; the second group received PG for 5 d + 24 g of oral NIA once per day for 3 d (PGNIA); and the third group received PG for 5 d + NIA for 3 d + 1.1 mg/kg i.v. FM once per day for 3 d (PGNIAFM). The control group consisted of cows that were clinically healthy (HC; untreated; BHB

Endotoxic shock was produced in 5 apparently healthy male buffalo calves aged between 4 month and 1 year by i/v infusion of Escherichia coil endotoxin @ 5 µg/kg BW/h for 3 h. The animals were further observed for 7 days. A general hypoproteinemia was observed during endotoxin infusion along with significant hypoalbuminemia, hypoglycemia, hypofibrinogenemia, decrease in plasma globulin, creatinine while plasma blood urea nitrogen, sodium, potassium, and chloride showed nonsignificant alterations during endotoxin infusion for 3 h. All the endotoxemic buffalo calves were infused i/v hypertonic saline solution (7.2% NaCI acq.) @ 4 ml/kg BW in 6.5 min followed by flunixin meglumine @ 1.1 mg/kg BW as one time infusion and plasma proteins showed a significant decrease at 4 h but increased significantly on day 2 while albumin showed a declining trend throughtout the observation period with a signigicant fall at 4 h of start of endotoxin infusion. While plasma globulin decreased, plasma fibrin increased significantly on second and third day. Hypoglycemia continued from day 1-6 accompanied by a nonsignificant fall in BHU within normal range throughtout the 7 day observation period. The plasma creatinine increased significantly at 5 and 7 h of day 1 and on day 2 of observation. Plasma sodium and chloride did not alter significantly indicating that this treatment combination does not greatly affect the biochemical profiles during bovine endotoxemia.

The in vivo metabolism and pharmacokinetics of flunixin meglumine and phenylbutazone have been extensively characterized; however, there are no published reports describing the in vitro metabolism, specifically the enzymes responsible for the biotransformation of these compounds in horses. Due to their widespread use and, therefore, increased potential for drug-drug interactions and widespread differences in drug disposition, this study aims to build on the limited current knowledge regarding P450-mediated metabolism in horses. Drugs were incubated with equine liver microsomes and a panel of recombinant equine P450s. Incubation of phenylbutazone in microsomes generated oxyphenbutazone and gamma-hydroxy phenylbutazone. Microsomal incubations with flunixin meglumine generated 5-OH flunixin, with a kinetic profile suggestive of substrate inhibition. In recombinant P450 assays, equine CYP3A97 was the only enzyme capable of generating oxyphenbutazone while several members of the equine CYP3A family and CYP1A1 were capable of catalyzing the biotransformation of flunixin to 5-OH flunixin. Flunixin meglumine metabolism by CYP1A1 and CYP3A93 showed a profile characteristic of biphasic kinetics, suggesting two substrate binding sites. The current study identifies specific enzymes responsible for the metabolism of two NSAIDs in horses and provides the basis for future study of drug-drug interactions and identification of reasons for varying pharmacokinetics between horses.

The current study radiographically and histologically evaluated the effects of meloxicam and flunixin meglumine on the repair of radial bone defects in a rabbit model. Ninety New Zealand White rabbits (10-12 months, 1.5-2.6 kg) were randomly assigned into three groups. Following anesthesia, defects were created on the medial surface of the radius bone of the left forelimb with a diameter and depth of 3 mm. The animals were administrated meloxicam, flunixin meglumine, and physiological serum (positive control) subcutaneously each day for 10 days. Hematoxylin and Eosin and Goldner’s trichrome stainings, along with radiograph images were prepared to investigate the effects of the administered agents. The results did not show callus formation in bone defects on days 3 and 7. Defects were filled in meloxicam and positive control groups on day 14, while they were filled on day 21 in the flunixin meglumine group. On days 14 and 21, the meloxicam group outperformed the flunixin meglumine group in terms of callus formation, but it was higher in the flunixin meglumine group on day 28. It could be concluded that the administration of meloxicam is less effective in delaying the bone healing process.

ABSTRACT: The objectives of this study were to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on serum concentrations of inflammatory and metabolic markers, uterine health, and indicators of pain. The hypothesis was that the anti-inflammatory, antipyretic, and analgetic effects of the pharmaceutic agent would reduce systemic inflammation, resulting in improved metabolic and inflammatory profile, diminished incidence of metritis, and reduced expression of pain. A total of 500 cows (153 primiparous, 347 multiparous) from 3 different commercial dairy farms in the northeast of Germany were included in a randomized controlled clinical trial. Farms were preselected based on high haptoglobin concentrations in their fresh lactating cows. Cows were excluded if they had experienced dystocia, stillbirth, or twin birth, or if they showed any signs of milk fever, retained fetal membranes, or fever (>40°C). The cows were treated once with either FM (3.33 mg/kg) or a placebo as control (CON) through transdermal administration between 24 to 36 h postpartum (d 2). General health examinations were performed (daily from d 2–8 and additionally on d 15 postpartum), vaginal discharge was assessed using the Metricheck device (d 8 and 15 postpartum) and serum samples were analyzed for inflammatory and metabolic markers (d 2, 4, and 6 postpartum). Effects of treatment, parity, sampling day, and their interactions were evaluated using mixed effects models. Primiparous cows treated with FM showed lower serum haptoglobin concentrations (0.90 ± 0.08 vs. 1.17 ± 0.07 g/L; ± standard error of the mean) and higher serum albumin concentrations (35.5 ± 0.31 vs. 34.8 ± 0.31 g/L) on d 6 postpartum. They also had a lower risk for purulent vaginal discharge with or without a fever compared with CON cows on d 15 postpartum (odds ratio for CON vs. FM: 1.63, 95% CI: 1.26–2.00), and body temperature was lower throughout the first 15 d in milk (39.1 ± 0.11 vs. 39.2 ± 0.11°C). Multiparous cows treated with FM had lower serum β-hydroxybutyrate concentrations on d 4 postpartum (0.71 ± 0.05 vs. 0.78 ± 0.05 mmol/L) and d 6 postpartum (0.74 ± 0.05 vs. 0.80 ± 0.05 mmol/L). Regardless of parity, FM-treated cows were significantly less likely to abduct their tail from their body (14.3 vs. 23.6%) and show an arched back (27.9 vs. 39.7%) on the day after treatment compared with CON cows. It can be concluded that FM treatment slightly reduced inflammation and diminished the risk for metritis in primiparous cows, improved metabolic profile in multiparous cows, and reduced expressions of pain in all cows.

ABSTRACT: This study was conducted to assess the effects of a single transdermal administration of flunixin meglumine (FM) in early postpartum Holstein Friesian dairy cows on milk yield, culling risk, and reproductive performance. We hypothesized that FM treatment would reduce systemic inflammation, leading to higher milk yield, reduced culling risk, and better reproductive performance in the subsequent lactation. Holstein Friesian dairy cows [n = 500, 153 primiparous (PRIM), 347 multiparous (MULT)] from 3 farms in northeast Germany were enrolled in a prospective, randomized controlled clinical trial. Farms at risk for cows with excessive postpartum inflammation were identified in a preliminary trial by measuring serum haptoglobin concentrations in their fresh lactating cows. Only cows that had a eutocic birth and delivered a singleton calf alive, with no signs of milk fever or retained fetal membranes and rectal temperature ≤40°C at first clinical examination, were included within 24 to 36 h postpartum. Treatment included a single transdermal administration of either FM (3.33 mg/kg) or a placebo as control (CON). Milk production, milk solids, urea, and somatic cell count were recorded monthly for 8 mo after calving. Culling risk, first-service conception risk, and days open were retrieved from the farms' herd management software. Separate models for PRIM and MULT cows were built for most parameters because of significant effects of parity and parity × treatment interaction. Energy-corrected milk yield from 8 monthly Dairy Herd Improvement-equivalent tests was slightly greater in PRIM cows treated with FM (29.51 and 30.73 ± 1.35 kg, CON vs. FM), whereas it was reduced in treated MULT cows (38.23 and 37.47 ± 1.17 kg, CON vs. FM) compared with CON. Milk fat and protein yields were greater in FM-treated PRIM cows and lower in treated MULT cows compared with CON. Milk urea and somatic cell count were not affected by treatment. No differences in culling risk, first-service conception risk, or days open were observed. We conclude that a single transdermal administration of FM in early postpartum dairy cows on farms at risk for excessive postpartum inflammation slightly increased milk, milk fat, and milk protein yields in PRIM cows and decreased these variables in MULT cows. Neither culling risk nor fertility was affected by treatment in this study.

This study was conducted to determine the impact of post-breeding administration of human chorionic gonadotropin hormone (hCG) and flunixin meglumine on luteal function and pregnancy rates in postpartum anoestrous Nili-Ravi buffaloes synchronized through a CIDR-GnRH based protocol during low breeding season. It was hypothesized that administering flunixin meglumine, an inhibitor of PGF2α synthesis, alone or in combination with hCG before implantation will increase the pregnancy rate by improving luteal functions in buffaloes. The sixty buffaloes (having a postpartum period of 90-120 days) were synchronized through the CIDR-GnRH protocol. Briefly, CIDR was placed intravaginally in all buffaloes for 7 days, then an injection of PGF2α was given on day 06 and GnRH on day 09. Timed artificial insemination (TAI) was done at 14-16 hrs following GnRH. After TAI, animals were randomly divided into four groups for different treatments. The T1 (n=15) buffaloes were given IM injection of hCG (3000 IU/animal) on day 07 after TAI. The T2 (n=15) buffaloes received an IM injection of flunixin meglumine (1.1mg/kg; b.i.d.) on days 14-15 post-TAI. The T3 (n=15) buffaloes received IM injections of hCG (3000 IU/animal) on day 07 and IM injection of flunixin meglumine (1.1mg/kg; b.i.d.) on day 14-15 post-TAI. In the T4 group (n=15), the control group received IM injection of normal saline on day 7 and day 14-15 after TAI. The size of the corpus luteum was measured by scanning ovaries through trans- rectal ultrasonog-raphy, and blood samples for serum progesterone assessment were collected on day 14 and day 20 post-TAI. Progesterone level was measured through ELISA. The pregnancy was diagnosed through ultrasonography on day 35 post-TAI. The results showed that the mean progesterone concentration was higher (p

Introduction: The study objectives were to estimate plasma flunixin (FLU) pharmacokinetic parameters and milk depletion profiles for FLU and its metabolite (5-hydroxy flunixin; 5-OH) after subcutaneous (SC) and intravenous (IV) administration of single and multiple flunixin meglumine (FM) doses to non-lactating (nulliparous and pregnant does) and lactating dairy goats. Analytical methods (ELISA and UPLC-MS/MS) for quantifying plasma FLU concentrations were compared. The final objective was to use regulatory (FDA and EMA) methods to estimate milk withdrawal intervals following extra-label drug use in goats. Methods: FM was administered IV and SC to commercial dairy goats at 1.1 mg/kg for single and multiple doses. Plasma and milk samples were analyzed for FLU and 5-OH via UPLC-MS/MS. Plasma samples were also analyzed for FLU concentrations via ELISA. Using statistical approaches recommended by regulatory agencies, milk withdrawal intervals were estimated following FM extra-label use. Results: Following IV administration of a single FM dose, clearances were 127, 199, and 365 ml/kg/h for non-lactating (NL) pregnant does, NL nulliparous does, and lactating dairy does, respectively. Following multiple SC doses, clearance/F was 199 ml/kg/h for lactating does. After IV administration of a single FM dose, terminal elimination half-lives were 4.08, 2.87, and 3.77 h for NL pregnant does, NL nulliparous does, and lactating dairy does, respectively. After multiple SC doses, the terminal elimination half-life was 3.03 h for lactating dairy does. No significant differences were noted for samples analyzed by UPLC-MS/MS or ELISA. Milk withdrawal intervals ranged from 36 to 60 h depending on the regulatory statistical method and dosage regimen. Conclusions: Subcutaneous administration of FM to goats results in similar plasma pharmacokinetic parameters as IV administration. ELISA analysis is an alternative method to UPLC-MS/MS for quantifying FLU concentrations in caprine plasma samples. Following FM extra-label administration to dairy goats, clinicians could consider 36-60 h milk withdrawal intervals.

ABSTRACT: The objective of this study was to evaluate the effect of the nonsteroidal anti-inflammatory drug transdermal flunixin meglumine (Finadyne Transdermal) on plasma cortisol, average daily weight gain, and standing and lying behavior of calves, when given at the time of disbudding combined with local anesthesia. A sedative was not used to minimize pharmacological interactions. Seventy-one female Holstein Friesian calves aged 13 ± 2 d, with an average weight of 48.9 ± 4.26 kg were enrolled in the study. All calves were randomly assigned to one of 3 treatment groups: (1) control group (CON, n = 27), (2) 1-flunixin group (1-FLU, n = 26) with a single administration of transdermal flunixin meglumine at disbudding, and (3) 2-flunixin group (2-FLU, n = 24) with 2 administrations of transdermal flunixin meglumine, the first treatment at disbudding and the second 6 h after disbudding. Although the CON group received a placebo, 1-FLU and 2-FLU received flunixin meglumine transdermally. To account for plasma cortisol changes due to manipulation and handling of the calves, a sham disbudding procedure was performed one week before disbudding took place. Sham disbudding was conducted by using a cold cautery dehorner applied to each horn bud for 10 s. Disbudding was performed in a similar way by using a hot cautery dehorner. Plasma samples were collected to measure the stress biomarker cortisol at 7 different time points. Body weights were measured 4 times in 2 wk. Standing and lying behavior was assessed via 3-dimensional accelerometer. During sham disbudding and disbudding mean plasma cortisol concentrations were 6.09 ± 2.5 ng/mL and 5.16 ± 2.8 ng/mL, respectively. Treatment tended to have an effect on plasma cortisol concentrations during sham disbudding and had an effect on plasma cortisol concentrations during disbudding. Plasma cortisol concentrations were affected by treatment 2 h after disbudding in comparison to CON group. Furthermore, there was a significant effect on plasma cortisol concentrations 6 h after disbudding in contrast to CON. A return to baseline plasma cortisol levels (initial concentrations) was not achieved in CON during disbudding. There was no statistical difference between average daily weight gain and the treatment procedure. Total lying time was not affected by treatment after disbudding. In conclusion, transdermal flunixin meglumine given at the time of disbudding combined with local anesthesia decreased concentrations of the stress biomarker cortisol, but a second dose 6 h after disbudding had no further effect on plasma cortisol levels.

The current study radiographically and histologically evaluated the effects of meloxicam and fl- unixin meglumine on the repair of radial bone defects in a rabbit model. Ninety New Zealand White rabbits (10-12 months, 1.5-2.6 kg) were randomly assigned into three groups. Following anesthesia, defects were created on the medial surface of the radius bone of the left forelimb with a diameter and depth of 3 mm. The animals were administrated meloxicam, flunixin meglumine, and physiological serum (positive control) subcutaneously each day for 10 days. Hematoxylin and Eosin and Goldner's trichrome stainings, along with radiograph images were prepared to investigate the effects of the administered agents. The results did not show callus formation in bone defects on days 3 and 7. Defects were filled in meloxicam and positive control groups on day 14, while they were filled on day 21 in the flunixin meglumine group. On days 14 and 21, the meloxicam group outperformed the flunixin meglumine group in terms of callus formation, but it was higher in the flunixin meglumine group on day 28. It could be concluded that the administration of meloxicam is less effective in delaying the bone healing process. [ABSTRACT FROM AUTHOR]

Two experiments were designed to investigate factors affecting the risk of pregnancy in recipient Holstein heifers after transfer of in vivo produced embryos. The first experiment determined interactions of donor (n=16, multiparous Holstein cows), recipient (n=95 heifers) and embryo associated factors contributing to pregnancy establishment in recipients. Donors were superstimulated using pFSH and embryos were collected on day 7 after insemination, graded and transferred fresh to synchronous recipients. Effects of donor superovulation response (SR, high vs. low), embryo quality grade (first, second or third) and circulating progesterone in recipients at ET (High vs. low) on pregnancy rate per embryo transfer (PR/ET) were evaluated. High SR of donors was associated with higher numbers of all embryo quality grades (P<0.05). Recipient heifers receiving 2nd and 3rd grade embryos from low SR donors achieved greater PR/ET (70%), compared to recipients receiving 2nd and 3rd grade embryos from high SR donors (17.65%). In experiment 2, recipient Holstein heifers were allocated into a control (n=48) and a flunixin meglumine (FM) treated group (n=21) in which individual heifers were administered with 10 ml FM at ET to test effects of FM on PR/ET. Recipient temperament was evaluated (calm vs excitable). Excitable recipient temperament at ET was associated with lower PR/ET. Pregnancy tended to be higher (66.67% vs 60.42%) in treated recipients. Conceivably, SR influenced establishment of pregnancy in recipients depending on the quality of transferred embryos. In addition, treatment of embryo recipients with FM at ET may improve PR/ET in excitable recipient dairy heifers. [ABSTRACT FROM AUTHOR]

Abstract A 12 week‐old Nigerian dwarf (Capra aegagrus hircus) buck kid was hospitalized for management of obstructive urolithiasis. Postoperatively, he was inadvertently administered 16‐times greater than his calculated dose of a nonsteroidal anti‐inflammatory drug (NSAID; 17.5 mg/kg flunixin meglumine, IV). The goat was treated with intravenous administration of lipid emulsion (ILE) prior to membrane‐based therapeutic plasma exchange (mTPE) under general anesthesia. The increased coagulability inherent to small ruminants in comparison with dogs and cats warranted specific adjustments in the prescription of anticoagulation, blood flow, and filtration fraction to avoid circuit clotting during mTPE. Serum flunixin meglumine concentration measured before, during, and after mTPE revealed marked reduction in drug concentration. After the combined treatments, no clinical evidence of NSAID gastrointestinal or renal toxicosis was detected. This case report describes successful management of flunixin meglumine overdose in a small ruminant using combined ILE and mTPE.

The objective of this study was to determine the effects of flunixin meglumine or meloxicam on behavioral response and performance characteristics associated with surgical castration in crossbred bulls. Intact male Bos taurus calves (n = 252; averaging 176 kg) were randomly allocated into one of three treatment groups within pen: control (CON), flunixin meglumine (FLU ; 2.2 mg/kg intravenous injection), or meloxicam (MEL ; 2.0 mg/kg per os). The individual animal was the experimental unit. Calves were individually weighed on days 0 and 14 of the trial to evaluate performance outcomes. On study day 0, treatments were administered, according to their random allocation, immediately prior to surgical castration using the Henderson tool method. Visual analog scale (VAS) assessment and categorical attitude score (CAS) were collected on days −1, 0 (6 h post-castration), 1, 2, 3, and 4 in the study. The VAS was assigned using a 100 mm horizontal line with "normal" labeled at one end of the line and "moribund" at the other end of the horizontal line. The masked observer assigned a mark on the horizontal line based upon the observed severity of pain exhibited by that individual animal. The CAS was assigned by the same observer using five different categories with a score of 0 being "normal". Average daily gain tended (P = 0.09) to be associated with the treatment group, and MEL had a greater (P = 0.04) average daily gain through day 14 compared with CON. A significant (P < 0.01) treatment by day interaction was indicated for VAS score, and MEL had lower VAS scores on days 0, 1, 2, and 3 post-castration compared with CON; FLU had lower VAS scores on days 0 and 1 compared with CON. A significant treatment by day interaction was not present (P = 0.25) for CAS. The FLU had lesser percent CAS ≥1 (17.5%; P = 0.05) compared with CON (29.4%); MEL has lesser percent CAS ≥1 observations (14.9%; P = 0.01) compared with CON. The median VAS increased as CAS was more severe. Results indicated MEL and FLU calves temporally improved behavioral responses following surgical castration with positive numerical trends for a 14 d average daily gain (ADG). The VAS system appeared to be an effective method of subjective evaluation of pain in beef calves in this study. Route of administration, duration of therapy, and low relative cost make oral meloxicam a reasonable analgesic treatment in calves when administered at the time of surgical castration. [ABSTRACT FROM AUTHOR]

ABSTRACT The aim of this study was to evaluate the effects of flunixin meglumine administration on pregnancy rates and luteal phase characteristics in bovine embryo recipients at the moment of embryo transfer. In experiment 1, in vitro produced embryos were transferred to 184 females divided as control and treated group (recipients treated with 1.1mg/kg flunixin meglumine). In experiment 2, 22 females were divided as control group; group 2 (animals submitted to a reproductive tract manipulation similar to an embryo transfer on the 7th day after estrous); and group 3 (females submitted to a manipulation and treatment with 1.1mg/kg flunixin meglumine). In experiment 1 no difference was observed between control and treated groups (40.2% and 44.6%, respectively) for pregnancy rates. In experiment 2 no difference was observed on the length of luteal phase between groups, however, animals in group 2 presented lower plasma progesterone concentrations than the control group and group 3. Therefore, we concluded that although the administration of flunixin meglumine at the moment of embryo transfer inhibited the reduction plasma progesterone concentrations, it was not effective in increasing pregnancy rates of bovine recipients.

Abstract Background Flunixin meglumine (FM) was investigated for the effectiveness of plasma, oral fluid, and urine concentrations to predict tissue residue depletion profiles in finishing-age swine, along with the potential for untreated pigs to acquire tissue residues following commingled housing with FM-treated pigs. Twenty pigs were housed in groups of three treated and one untreated control. Treated pigs received one 2.2 mg/kg dose of FM intramuscularly. Before treatment and at 1, 3, 6, 12, 24, 36, and 48 h (h) after treatment, plasma samples were taken. At 1, 4, 8, 12 and 16 days (d) post-treatment, necropsy and collection of plasma, urine, oral fluid, muscle, liver, kidney, and injection site samples took place. Analysis of flunixin concentrations using liquid chromatography/tandem mass spectrometry was done. A published physiologically based pharmacokinetic (PBPK) model for flunixin in cattle was extrapolated to swine to simulate the measured data. Results Plasma concentrations of flunixin were the highest at 1 h post-treatment, ranging from 1534 to 7040 ng/mL, and were less than limit of quantification (LOQ) of 5 ng/mL in all samples on Day 4. Flunixin was detected in the liver and kidney only on Day 1, but was not found 4–16 d post-treatment. Flunixin was either not seen or found less than LOQ in the muscle, with the exception of one sample on Day 16 at a level close to LOQ. Flunixin was found in the urine of untreated pigs after commingled housing with FM-treated pigs. The PBPK model adequately correlated plasma, oral fluid and urine concentrations of flunixin with residue depletion profiles in liver, kidney, and muscle of finishing-age pigs, especially within 24 h after dosing. Conclusions Results indicate untreated pigs can be exposed to flunixin by shared housing with FM-treated pigs due to environmental contamination. Plasma and urine samples may serve as less invasive and more easily accessible biological matrices to predict tissue residue statuses of flunixin in pigs at earlier time points (≤24 h) by using a PBPK model.

Case Description- A five-year-old Arabian stallion weighing approximately 300 kg with large infected chronic torn wound on the neck and pectoral region 5 days after IM injection of flunixin meglumine with history of anorexia, depression and lack of response to antibacterial treatment referred to the Veterinary Teaching Hospital of Lorestan University. Clinical Findings- The clinical symptoms observed during the examination were hematuria and watery diarrhea with very large skin laceration in the affected area. External examination revealed the infectious cervical and pectoral muscles and necrosed skin with purulent discharge and odorous smell. Skin and surrounding tissues were warm, edematous and swelled.Treatment and Outcomes- Surgical treatment started with physical debridement and maggot therapy using Lucilia (Phaenicia) sericata. Then medical treatment continued with intravenous fluid therapy, antimicrobial and anti-inflammatory drugs (NSAID) along with topical treatment. Clinical Relevance- The present case demonstrates the serious complications that can occur following non-sterile IM injections and/or as a consequence of flunixin meglumine IM administration. An aggressive pharmacological and surgical therapy is very essential in similar cases. In conclusion, successful management of the cutaneo-muscular necrosis depends upon the condition of wound and selection of proper antibacterial drugs along with early surgical intervention.

Aim: In the present study; the effects of flunixin meglumine application on the fertility of synchronized Awassi ewes was investigated during breeding season. Materials and Methods: In this study 100 multiparous Awassi ewes, aged 2-4, housed in the same care and feeding conditions used. For this purpose, 30 mg fluorogesteron acetate vaginal sponge placed into the vagina during the breeding season (September- October). On the 11th days after insertion of sponge, 10 mg PGF2? intramuscularly administered. Vaginal sponges withdrawn on day 12 and administered with 400 IU PMSG intramuscularly. Following intramuscular PMSG injection the ewes which show estrus sign joined to known fertility rams. The animals were allocated into two equal groups as treatment and control. Flunixin meglumine applied i.m at the dose of 1.1 mg / kg on the 9th day and on the 10th day post mating (n = 50) included in the treated group. No treatment made to the ewes (n = 50) included in the control group. The pregnancy diagnosis was performed by trans-abdominal route by real time ultrasonography on day 50 after mating. Results: The rate of conception in the treated and control groups was 40.9 % and 33.3 %, respectively (p >0.05). The rate of lambing in treated and control groups was 77.7 % and 87.5 %, respectively (p >0.05). Conclusion: The application of flunixin meglumine on the 9th and 10th days after breeding in Awasi ewes only increased the rate of conception numerically. However, it can be considered to increase conception rate in alternative options such as artificial insemination and embryo transfer.

ABSTRACT: Excessive infection and inflammation are the most common complications associated with castration. The objective of this study was to compare the efficacy of flunixin meglumine (FM), meloxicam (MX), or firocoxib (FX) for inflammation control after castration in horses using acute-phase proteins (APP) as markers of inflammation. Thirty healthy, unbroken, mixed-breed horses (body weight 358.62±45.57kg and age 4.99±2.63 years) were randomly (n=10 animals/group) allocated to receive one of three different post-castration anti-inflammatory medicines: Group 1 (FM 1.1mg/kg bwt, IV, s.i.d for 5 days); Group 2 (MX 0.6mg/kg bwt, IV, s.i.d for 5 days); and Group 3 (FX 0.1mg/kg bwt, IV, s.i.d for 5 days). All horses were castrated in standing position, using the open technique. Serum and peritoneal APP concentrations were measured by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis (PAGE) and determined before castration (0), and 3, 5, 24, 48, 72, 120 and 168 hours after castration. The results were submitted to analysis of variance using the SAS statistical program, and means were compared by the Student-Newman-Keuls test (p

Abdominal adhesions following abdominopelvic surgical interventions are well-known causes of increased morbidity and mortality during the postoperative period. In this study, it was aimed to investigate the effects of flunixin meglumine and amnion fluid on the prevention of intraabdominal adhesions. Twenty-one rats were used in this study. The rats were divided into 3 groups as 7 rats in each group. An adhesion model was formed by performing a scraping process on the visceral surface of the abdominal wall and caecum until serosal hemorrhage occurred. One split two ml saline, 2.5 mg/kg flunixin meglumine and 0.5 ml amnion fluid were injected intraperitoneally to the rats in the control, flunixin and amnion groups for 5 days respectively. After 14 days, rats received general anesthesia and occurred adhesions were graded. At the end of the 14th day, rats in all groups were euthanized. In macroscopic evaluation, adhesion formation in treatment groups was less than in the control group (P<0.05). Immunohistochemical results are presented in tables. As a result, it was concluded that flunixin meglumine and amnion fluid could be used in the prevention of intraabdominal adhesions. [ABSTRACT FROM AUTHOR]

A 12 week‐old Nigerian dwarf (Capra aegagrus hircus) buck kid was hospitalized for management of obstructive urolithiasis. Postoperatively, he was inadvertently administered 16‐times greater than his calculated dose of a nonsteroidal anti‐inflammatory drug (NSAID; 17.5 mg/kg flunixin meglumine, IV). The goat was treated with intravenous administration of lipid emulsion (ILE) prior to membrane‐based therapeutic plasma exchange (mTPE) under general anesthesia. The increased coagulability inherent to small ruminants in comparison with dogs and cats warranted specific adjustments in the prescription of anticoagulation, blood flow, and filtration fraction to avoid circuit clotting during mTPE. Serum flunixin meglumine concentration measured before, during, and after mTPE revealed marked reduction in drug concentration. After the combined treatments, no clinical evidence of NSAID gastrointestinal or renal toxicosis was detected. This case report describes successful management of flunixin meglumine overdose in a small ruminant using combined ILE and mTPE. [ABSTRACT FROM AUTHOR]

Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2.2 mg/kg for IV and IM and 3.3 mg/kg for PO and TD route. Plasma was collected at twenty-seven time points from 0 to 9 days after FM administration and concentrations were determined using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Pharmacokinetic data were analyzed using noncompartmental analysis (NCA) methods and nonlinear mixed-effects (NLME). Initial plasma concentration for IV (C0) 11,653 μg/L and mean peak plasma concentrations (Cmax) 6,543 μg/L (IM), 4,883 μg/L (PO), and 31.5 μg/L (TD) were measured. The time points of peak FM concentrations (tmax) were estimated 30 min, 1 h, and 24 h for IM, PO, and TD, respectively. The bioavailability (F) of PO and IM FM was estimated at >99%, while the bioavailability of TD FM was estimated to be 7.8%. The reported Cmax of FM after IM and PO administration is consistent with therapeutic concentration ranges that mitigate pain in other species and adult pigs. However, the low estimated concentration of FM after TD dosing is not expected to mitigate pain in pre-wean piglets. The low F of TD FM suggests that expanding the surface area of application is unlikely to be sufficient to establish an effective TD dose for pain, while the high bioavailability for PO FM should allow for an effective dose regimen to be established.

Introduction: The study objectives were to estimate plasma flunixin (FLU) pharmacokinetic parameters and milk depletion profiles for FLU and its metabolite (5-hydroxy flunixin; 5-OH) after subcutaneous (SC) and intravenous (IV) administration of single and multiple flunixin meglumine (FM) doses to non-lactating (nulliparous and pregnant does) and lactating dairy goats. Analytical methods (ELISA and UPLC-MS/MS) for quantifying plasma FLU concentrations were compared. The final objective was to use regulatory (FDA and EMA) methods to estimate milk withdrawal intervals following extra-label drug use in goats.Methods: FM was administered IV and SC to commercial dairy goats at 1.1 mg/kg for single and multiple doses. Plasma and milk samples were analyzed for FLU and 5-OH via UPLC-MS/MS. Plasma samples were also analyzed for FLU concentrations via ELISA. Using statistical approaches recommended by regulatory agencies, milk withdrawal intervals were estimated following FM extra-label use.Results: Following IV administration of a single FM dose, clearances were 127, 199, and 365 ml/kg/h for non-lactating (NL) pregnant does, NL nulliparous does, and lactating dairy does, respectively. Following multiple SC doses, clearance/F was 199 ml/kg/h for lactating does. After IV administration of a single FM dose, terminal elimination half-lives were 4.08, 2.87, and 3.77 h for NL pregnant does, NL nulliparous does, and lactating dairy does, respectively. After multiple SC doses, the terminal elimination half-life was 3.03 h for lactating dairy does. No significant differences were noted for samples analyzed by UPLC-MS/MS or ELISA. Milk withdrawal intervals ranged from 36 to 60 h depending on the regulatory statistical method and dosage regimen.Conclusions: Subcutaneous administration of FM to goats results in similar plasma pharmacokinetic parameters as IV administration. ELISA analysis is an alternative method to UPLC-MS/MS for quantifying FLU concentrations in caprine plasma samples. Following FM extra-label administration to dairy goats, clinicians could consider 36–60 h milk withdrawal intervals.

Both the economic loss and welfare implications of lameness affect the dairy industry. Currently no analgesic drugs are approved to alleviate lameness-associated pain in lactating dairy cattle in the United States. In this randomized controlled trial, 48 lactating Holsteins were enrolled to evaluate the effect of oral meloxicam and i.v. flunixin meglumine on induced lameness. Cows were allocated to 1 of 4 treatment groups (n = 12 per group): lameness and flunixin meglumine (LAME + FLU); lameness and meloxicam (LAME + MEL); lameness and placebo (LAME + PLBO); or sham induction and placebo (SHAM + PLBO). Six hours before treatment, arthritis-synovitis was induced in the distal interphalangeal joint with 20 mg of amphotericin B, whereas SHAM cows were given an intra-articular injection of an equal volume (4 mL) of isotonic saline. Cows in LAME + FLU received 2.2 mg/kg flunixin meglumine i.v. and whey protein placebo orally; LAME + MEL were administered 1 mg/kg meloxicam orally and 2 mL/45 kg sterile saline placebo i.v.; LAME + PLBO were administered 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally; and SHAM + PLBO received 2 mL/45 kg sterile saline placebo i.v. and whey protein placebo orally. The initial treatment of MEL, FLU, or PLBO was identified as time 0 h and followed by a second dose 24 h later with data collection for 120 h. The methods used to assess analgesic efficacy were electronic pressure mat, visual lameness assessment, visual analog score, plasma cortisol concentration, plasma substance P concentration, mechanical nociception threshold, and infrared thermography imaging. Linear mixed effect modeling was the primary method of statistical analysis. Visual lameness scoring indicated a lower proportion of the FLU + LAME group was lame at the T2 h and T8 h time points in comparison to the positive controls, whereas MEL therapy resulted in a lower proportion of lame cows at the T8 h time point. Cortisol area under the effect curve was lower following FLU therapy compared with LAME + PBLO for the 0–2 h (LSM difference = 35.1 ng·h/mL, 95% CI: 6.8, 63.3 ng·h/mL), 2–8 h (LSM difference = 120.6 ng·h/mL, 95% CI: 77.2, 164.0 ng·h/mL), and 0–24 h (LSM difference = 226.0 ng·h/mL, 95% CI: 103.3, 348.8 ng·h/mL) time intervals. Following MEL therapy, cortisol area under the effect curve was lower than LAME + PLBO for both the 2 to 8 h (LSM difference = 93.6 ng·h/mL, 95% CI: 50.2, 137.0 ng·h/mL) and 0 to 24 h time intervals (LSM difference = 187.6 ng·h/mL, 95% CI: 64.9, 310.4 ng·h/mL). Analysis of data from other assessment modalities failed to discern biologically relevant differences between treatment groups. We conclude that meaningful differences were evident for visual lameness assessment and cortisol from MEL and FLU treatment versus the positive control. Further clinical research is needed toward development of a model that will create reproducible events that are more pronounced in severity and duration of lameness which can be validated as a substitute for naturally occurring lameness cases. [ABSTRACT FROM AUTHOR]

The aim of this study was to correlate the serum levels of acute phase proteins (APPs) and cytokines in response to treatment by various antimicrobial agents in feedlots calves (FL) naturally infected with Mannheimia haemolytica (M. haemolytica) and Histophilus somni (H. somni). 840 feedlot calves in one farm in Al-Kharg region, Saudi Arabia were clinically examined for the presence of respiratory disease manifestations. The infection was confirmed using nasopharyngeal swabs. Blood samples from diseased animals were collected before and after (7 days) treatment for biochemical analysis of serum amyloid A (SAA), haptoglobin (HP) and cytokines tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ), interleukin-1 β (IL- 1β), and interleukin-8 (IL-8). FL that were positive for M. haemolytica and/or H. somni (n=69) received treatment with one antibiotic, including tulathromycin (Tula; n=26 cases), florfenicol (FFC; n=19), tilmicosin (Tm; n=13), or ceftiofur (CEF; n=11) and one non-steroidal anti-inflammatory drug (Flunixin meglumine (FM; n=43) or phenylbutazone (PBZ; n= 26). We demonstrated the selective potent inhibitory effect of the administrated anti-inflammatory agents either FM or PBZ on the production of APPs and pro-inflammatory cytokines in FL infected with bovine respiratory disease (BRD). Our findings showed the antibacterial efficacy of FFC and Tm for the treatment of infected FL when administrated with either FM or PBZ. However, Tula was preferable to administrate in combination with FM for the treatment of FL with respiratory manifestations. Importantly, monitoring the sera level of Hp, IL-1ß, and interleukin-8 (IL-8) in feedlots treated with either FM combined with Tula, FFC, or Tm or PBZ combined with FFC, and Tm has been effective in predicting the disease prognosis. [ABSTRACT FROM AUTHOR]

Background: Flunixin meglumine (FM) was investigated for the effectiveness of plasma, oral fluid, and urine concentrations to predict tissue residue depletion profiles in finishing-age swine, along with the potential for untreated pigs to acquire tissue residues following commingled housing with FM-treated pigs. Twenty pigs were housed in groups of three treated and one untreated control. Treated pigs received one 2.2 mg/kg dose of FM intramuscularly. Before treatment and at 1, 3, 6, 12, 24, 36, and 48 h (h) after treatment, plasma samples were taken. At 1, 4, 8, 12 and 16 days (d) post-treatment, necropsy and collection of plasma, urine, oral fluid, muscle, liver, kidney, and injection site samples took place. Analysis of flunixin concentrations using liquid chromatography/tandem mass spectrometry was done. A published physiologically based pharmacokinetic (PBPK) model for flunixin in cattle was extrapolated to swine to simulate the measured data. Results: Plasma concentrations of flunixin were the highest at 1 h post-treatment, ranging from 1534 to 7040 ng/mL, and were less than limit of quantification (LOQ) of 5 ng/mL in all samples on Day 4. Flunixin was detected in the liver and kidney only on Day 1, but was not found 4–16 d post-treatment. Flunixin was either not seen or found less than LOQ in the muscle, with the exception of one sample on Day 16 at a level close to LOQ. Flunixin was found in the urine of untreated pigs after commingled housing with FM-treated pigs. The PBPK model adequately correlated plasma, oral fluid and urine concentrations of flunixin with residue depletion profiles in liver, kidney, and muscle of finishing-age pigs, especially within 24 h after dosing. Conclusions: Results indicate untreated pigs can be exposed to flunixin by shared housing with FM-treated pigs due to environmental contamination. Plasma and urine samples may serve as less invasive and more easily accessible biological matrices to predict tissue residue statuses of flunixin in pigs at earlier time points (≤24 h) by using a PBPK model. [ABSTRACT FROM AUTHOR]

Hoof trimming is used to prevent and treat lameness in dairy cows; however, hoof trimming itself increases daily time spent lying down, possibly due to discomfort. We hypothesized that treatment of lame and nonlame cows with an anti-inflammatory analgesic drug at the time of hoof trimming would mitigate discomfort, thereby improving locomotion scores and reducing post-trimming increases in lying time. We further hypothesized that drug treatment would improve post-trimming milk production. Our objective was to determine the effects of treatment with the nonsteroidal anti-inflammatory drug flunixin meglumine (2.2 mg/kg of BW) at the time of hoof trimming on locomotion, lying times, and milk production in lame and nonlame lactating dairy cows. All cows were filmed for locomotion scoring 1 d before and 1, 8, and 28 d after hoof trimming. Daily time spent standing and lying was recorded for 4 d before and 4 wk after hoof trimming, and daily milk production was recorded for 1 wk before and 8 wk after trimming. Thirty minutes before hoof trimming, an intravenous injection of flunixin meglumine (n = 34) or isotonic sterile saline solution (n = 34) was administered to each cow. Then, all cows had their hooves trimmed using the Dutch method. The same treatment was repeated 24 h after hoof trimming. Cows were categorized using baseline locomotion scores as lame (score ≥3/5) or nonlame (score <3/5). Drug treatment did not affect post-trimming changes in locomotion scores, daily lying times, or milk production. In both treatment groups, most cows had the same lameness status (lame or nonlame) at baseline and after treatment, and there was no difference between groups in the number of cows that changed lameness status over time. Lame cows (n = 21) had no significant changes in lying times over the course of the study, whereas nonlame cows (n = 47) had mean daily lying times that were significantly higher than baseline all 4 wk after trimming. Hoof trimming in nonlame cows should be scheduled for a time when increased lying behavior after trimming can be accommodated. [ABSTRACT FROM AUTHOR]

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Flunixin meglumine (FM) is a novel nonsteroidal anti-inflammatory drug for animals, which has antipyretic, analgesic, and anti-inflammatory effects. The drug, which was originally used to relieve inflammation in horses, musculoskeletal disorders, and pain, has been approved for use in endotoxemia, infectious diseases in swine, etc. A sensitive anti-FM monoclonal antibody 2H4 was prepared and used to develop an indirect competitive enzyme-linked immunosorbent assay and immunochromatographic strip assay for the detection of FM in milk. The complete antigen and coating antigen were conjugated with bovine serum albumin and ovalbumin, respectively. The monoclonal antibody 2H4, with a half inhibition concentration of 0.29 ng/mL, had a limit of detection of 0.432 ng/mL and a linear range of detection of 0.08664–0.97226 ng/mL. A sensitive and convenient immunochromatographic strip assay was developed with an FM cutoff value of 0.29 ng/mL. The developed methods were suitable for the detection of FM in milk.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most commonly used postoperative analgesics, antipyretics, and anti-inflammatories, and they help prevent blood clotting. However, most NSAIDs delay bone healing. This study was aimed to investigate bone healing in a rabbit animal model by assessing the ability of flunixin meglumine (FM) and ketoprofen to induce fracture healing by examining histology, radiological changes, and vascular endothelial growth factor (VEGF) immunostaining during bone healing. For this purpose, 24 New Zealand rabbits were assigned to three groups: the control group, the FM group, and the ketoprofen group. Our results revealed that there were no intraoperative complications, and all surviving rabbits achieved full-weight bearing. Significant periosteal reaction and callus formation were confirmed at 2 postoperative weeks. Interestingly, FM enhanced callus formation, bone union, and remodeling in the FM group compared to the control and ketoprofen groups. FM enhanced bone healing through early collagen deposition and marked angiogenesis process activation by increasing the expression of VEGF. Our findings demonstrated, for the first time, the potential imperative action of FM in the bone healing process rather than other NSAIDs in animals.

Early regression of the corpora lutea (ERCL) reduces the efficiency of multiple ovulation and embryo transfer (MOET) programs in small ruminants. The objective of this study was to evaluate the effect of Flunixin meglumine (FM) and human chorionic gonadotropin (hCG) on embryo recovery in sheep superovulated with FSH and eCG and pregnancy rate in recipients. The study was divided into two parts. In Trial 1, 12 donors were divided into three groups i.e. Control, FM group (1.1mg FM/kg, SID, from artificial insemination-AI until embryo collection) and hCG group (1000UI hCG, 84 hours after progesterone device withdrawal). The mean ± standard error of the quantity of corpus luteum (CL) and the quantity and quality of the recovered embryos were analyzed. In Trial 2, 34 donors were divided into two groups i.e. Control and FM, the mean ± standard error of the quantity of recovered embryos were evaluated. Fifty-four embryos from each group in trial 2 were transferred into recipients and pregnancy rate was analyzed. In Trial 1, there were more (P <0.05) CL in the FM group than in the control and hCG groups, however there was no difference in embryo quantity or quality. In Trial 2 there was no significant difference in the number of CL or embryos recovered, nor in the pregnancy rate after embryo transfer. In conclusion, the strategies used in the prevention of ERCL had no effect on embryo recovery or embryo survival. [ABSTRACT FROM AUTHOR]

Copyright of Eurasian Journal of Veterinary Sciences is the property of Eurasian Journal of Veterinary Sciences and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The present study was designed to study the effect of flunixin meglumine following embryo transfer during luteal phase of estrous cycle on Prostaglandin fetal metabolite (PGFM) and progesterone in embryo recipient cows. Eighteen crossbred cows were selected and divided into three groups; Control (n=6): NSS, T-I (n=6): flunixin meglumine @ dose rate of 1.1 mg/kg half-hour before transfer, T-II (n=6): flunixin meglumine @ dose rate of 1.1 mg/kg half-hour before transfer and on Day 16 and Day 17 of oestrous cycle. Blood samples were collected on 7½ day of oestrous cycle without any treatment i.e. before embryo transfer and then half an hour after treatment. Again blood samples were taken at 15 minute, 50 minute and 150 minute following embryo transfer, On day 16, 17 and 18 of estrous cycle, blood sampling was done every 12 hour and for progesterone estimation blood samples were taken before treatment/ transfer, 150 min after transfer/treatment then on 16th, 17th, 18th, and 32nd day following estrus. Results of the study showed that the PGFM level and progesterone level differ non-significantly (p>0.05) between the groups but after treatment, there was marked decrease in PGFM level and simultaneously increased progesterone concentration. Out of three pregnancies, one animal aborted on day 76 of gestation. On the basis of above findings, it may be concluded that administration of flunixin meglumine during luteal phase of estrous cycle may be beneficial in improving the conception following embryo transfer in crossbred cattle as evident by decreased level of PGFM and increased level of progesterone during critical days of maternal recognition of pregnancy. [ABSTRACT FROM AUTHOR]

Dysfunctional inflammation contributes significantly to the pathogenesis of coliform mastitis and the classical pro-inflammatory enzyme cyclooxygenase-2 (COX-2) is the target of medical intervention using the non-steroidal anti-inflammatory drug (NSAID) flunixin meglumine (FM). Inhibition of COX-2 by FM can decrease concentrations of pro-inflammatory fatty acid-based mediators called eicosanoids, providing antipyretic and analgesic effects in dairy cows suffering from coliform mastitis. However, approximately 50% of naturally occurring coliform mastitis with systemic involvement results in death of the animal, even with NSAID treatment. Inadequate antioxidant potential (AOP) to neutralize reactive oxygen species (ROS) produced during excessive inflammation allows for oxidative stress (OS), contributing to tissue damage during coliform mastitis. Biomarkers of lipid peroxidation by ROS, called isoprostanes (IsoP), were used in humans and cattle to quantify the extent of OS. Blood IsoP were shown to be elevated and correlate with oxidant status during acute coliform mastitis. However, the effect of FM treatment on oxidant status and markers of OS has not been established. Blood IsoP concentrations were used to quantify systemic OS, whereas milk was used to assess local OS in the mammary gland. Results indicate that FM treatment had no effect on blood markers of inflammation but reduced the oxidant status index (OSi) by increasing blood AOP from pre- to post-FM treatment. Milk AOP significantly increased from pre- to post-FM treatment, whereas ROS decreased, resulting in a decreased OSi from pre- to post-FM treatment. The only blood IsoP concentration that was significantly different was 5-iso-iPF2α-VI, with a decreased concentration from pre- to post-FM treatment. Conversely, milk 5-iso-iPF2α-VI, 8,12-iso-iPF2α-VI, and total IsoP concentrations were decreased following FM treatment. These results indicated that administration of FM did improve systemic and local oxidant status and reduced local markers of OS. However, differential effects were observed between those animals that survived the infection and those that died, indicating that pre-existing inflammation and oxidant status greatly affect efficacy of FM and may be the key to reducing severity and mortality associated with acute coliform infections. Supplementation to improve AOP and anti-inflammatory mediator production may significantly improve efficacy of FM treatment.

This study investigated whether the L-arginine-NO system participates in the analgesic effect of flunixin meglumine in the rat. Hyperalgesia was induced by intraplantar (i.pl.) administration of carrageenan (500 μg) into the rat’s hind paw. Electronic von Frey apparatus was used to determine paw withdrawal threshold induced by pressure as the painful stimulus, measured in grams (g). Flunixin meglumine (FM; 0.09-0.1 mg/kg; s.c.) and NG-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg; i.p.), given separately as a pre-treatment, i.e. 15 min before i.pl. injection of carrageenan, produced a significant antinociception. When FM (0.09 mg/kg) and a sub-effective dose of L-NAME (5 mg/kg) were co-administered, the antinociceptive effect was significantly increased in comparison with the effect of FM alone. L-arginine (L-ARG;10 mg/kg; i.p.) itself did not produce significant effect on carrageenan-induced hyperalgesia, but significantly reduced the antinociceptive effects of both FM and FM + L-NAME combination. The inhibition of the production of NO might be involved in the mechanism of the analgesic effect of FM.

The amount of scientific data evaluating sheep pain responses after analgesia treatment is limited. The aims of this study were to compare the efficacy of flunixin meglumine (FLU) and meloxicam (MEL) at relieving post-surgical pain in sheep and to evaluate the utility of the Sheep Grimace Scale (SGS). Thirty ewes were assigned to one of three treatment groups: oral MEL or intravenous FLU to manage pain associated with a laparotomy procedure, or a non-surgical control (CON) group. Behavior and physiologic outcome measures were collected pre-procedure and up to 48 h post-procedure. There were no significant differences in behavior, gait, degree of inflammation or pain around the surgical site when MEL and FLU sheep were compared, suggesting that both drugs provided similar levels of analgesia. Significant differences in behavior, gait, abdominal inflammation and pain were found when surgical sheep were compared to non-surgical controls. More work is needed to characterize the amount of pain relief provided by MEL and FLU. The SGS had moderate reliability between scorers; however, the results were inconsistent with the other study outcome measures. The SGS may have some utility as a pain assessment tool but should be used in conjunction with other pain measures.

Objective- This research was conducted to study the effect of flunixin meglumine and ketoprofen on the healing of excisional wounding in the tendon of rats. Design- Experimental study. Animals- Twenty rats were equally divided into four groups of control, placebo (excised tendon receiving saline solution), flunixin and ketoprofen. Procedures- Right Achill complex of all groups underwent full thickness tenotomy. All the rats, except control group, received normal saline, flunixin meglumine or ketoprofen, respectively after operation for 7 days. After euthanasia of all animals on the day 15, the Achill complex was dissected free and prepared for histopathologic study. Neovascularization, edema and inflammatory cell infiltration, fibrin layer formation as well as fibroblast and fibrocyte counts were considered for the evaluation of healing process. Neovascularization, edema and inflammatory cell infiltration were scored from 0 to 3. Results- Results showed no significant change in number of fibroblasts between the groups. Reduced angiogenesis in both treatment groups of non-steroidal anti-inflammatory drugs (NSAIDs) was observed. Conclusion and Clinical Relevance- Our findings showed that anti inflammatory effects of ketoprofen is slightly more potent than flunixin meglumine, although differences were not statistically significant.

Flunixin meglumine (FM) is a novel nonsteroidal anti-inflammatory drug for animals, which has antipyretic, analgesic, and anti-inflammatory effects. The drug, which was originally used to relieve inflammation in horses, musculoskeletal disorders, and pain, has been approved for use in endotoxemia, infectious diseases in swine, etc. A sensitive anti-FM monoclonal antibody 2H4 was prepared and used to develop an indirect competitive enzyme-linked immunosorbent assay and immunochromatographic strip assay for the detection of FM in milk. The complete antigen and coating antigen were conjugated with bovine serum albumin and ovalbumin, respectively. The monoclonal antibody 2H4, with a half inhibition concentration of 0.29 ng/mL, had a limit of detection of 0.432 ng/mL and a linear range of detection of 0.08664-0.97226 ng/mL. A sensitive and convenient immunochromatographic strip assay was developed with an FM cutoff value of 0.29 ng/mL. The developed methods were suitable for the detection of FM in milk. [ABSTRACT FROM AUTHOR]

Thirty-six Sprague Dawley male rats were housed in individual cages and randomly divided into six groups: control, copper sulfate (Cu; 500 ppm body weight (BW)/day), flunixin meglumine (FM; 2.2 ppm BW/day), chrysin (chrysin; 50 ppm BW/day), copper sulfate + FM (Cu + FM; 500 ppm BW/day of copper sulfate and 2.2 ppm BW/day of FM), and copper sulfate + chrysin (Cu + Chrysin; 500 ppm BW/day of copper sulfate and 50 ppm BW/day of chrysin). Feed intake (FI) in the Cu + Chrysin group significantly increased in comparison with that of the Cu group (P < 0.01). Cu excess significantly increased malondialdehyde, indicating oxidative stress. Chrysin and FM administration significantly decreased malondialdehyde levels and increased the superoxide dismutase and catalase activities in the liver and kidney tissues (P < 0.001). Serum TNF-a levels were significantly lower in the Cu + FM and Cu + Chrysin groups in comparison to the Cu group (P < 0.001). It was seen that FM and chrysin treatments alleviated degeneration, necrosis, and apoptosis in the liver and kidney tissues of the Cu-treated rats. Chrysin appeared to ameliorate the adverse effects on FI and liver and kidney tissues by scavenging where the free radicals are located and increasing the activity of antioxidants. [ABSTRACT FROM AUTHOR]

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