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Flunixin meglumine is a nonsteroidal anti-inflammatory drug (NSAID). Banamine Transdermal is a pour-on formulation of flunixin approved for pain control in beef and dairy cattle, but not for calves and some classes of dairy cattle or swine. Violative flunixin residues in edible tissues in cattle and swine have been reported and are usually attributed to non-compliant drug use or failure to observe an appropriate withdrawal time. This project aimed to develop a physiologically based pharmacokinetic (PBPK) model for flunixin in cattle and swine to predict withdrawal intervals (WDI) after exposures to different therapeutic regimens of Banamine Transdermal. Due to the lack of comprehensive skin physiological data in cattle, the model was initially developed for swine and then adapted for cattle. Monte Carlo simulation was employed for population variability analysis. The model predicted WDIs were rounded to 1 and 2 d for liver and muscle in cattle, respectively, under FDA tolerance levels, while under EU maximum residue limits, the WDIs were rounded to 1, 3, 2, and 2 d for liver, kidney, muscle, and fat, respectively, following a labeled single transdermal 3.3 mg/kg dose in cattle. The model was converted into a user-friendly interactive PBPK (iPBPK) interface. This study reports the first transdermal absorption model for drugs in cattle. This iPBPK model provides a scientifically based tool for the prediction of WDIs in cattle and swine administered with flunixin in an extra-label manner, especially by the transdermal route. [ABSTRACT FROM AUTHOR]

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]

This study investigated the hematological parameters and renal function effects of Flunixin Meglumine (FM) and assessed the potential protective role of Alpha lipoic acid (ALA) in male rats. Hematological studies, kidney function tests, oxidative stress and antioxidant capacities, kidney weights and index weights, and histopathological studies were evaluated on the 4th and 8th weeks of the experiment. The experiment involved administering FM for 14 successive days and ALA for 56 successive days. Seventy-two (72) male rats were randomly divided into six groups (n=12 animals each): Group 1 (control) received saline and distilled water, Group 2 (ALA) received ALA at a dose level 100mg/kg bwt orally, Group 3 (FM-2.5) received Flunixin meglumine at a dose level (2.5mg/kg bwt) subcutaneously, Group 4 (FM-5) received FM subcutaneously, Group 5 (FM-2.5 and ALA) received FM and ALA, and Group 6 (FM-5 and ALA) received FM and ALA. Flunixin meglumine increased WBCs, serum urea and creatinine levels, MDA, some histopathological changes in kidney tissue, and decreased TAC. These alterations were mitigated by addition of alpha lipoic acid. Non-significant changes in Hb (g/dl), PCV%, RBCs and kidney index weight among all treated and control groups. In conclusion, the administration of FM induced hematological and renal impairments in male rats. However, co-administration of ALA effectively mitigated these impairments, suggesting its potential protective role against FM-induced hematological and renal disturbances. [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.

Green analytical chemistry is an important area of chemical sciences. So, developing competent eco-friendly analytical tools is a big challenge. This study devotes two chromatographic techniques for the simultaneous determination of a binary formulated mixture of oxytetracycline HCl (OXY) and flunixin meglumine (FLU), and their impurities tetracycline (TRC) and 2-chloronicotinic acid (CNA), respectively. Primarily, a TLC densitometric method is proposed and validated using TLC plates sprayed with 5% EDTA of pH 9 as a stationary phase and (acetonitrile/ distilled water/ ethanol 7:2:1, by volume) as a developing system. Well-separated spots are detected at 267 nm where linear relations have been achieved at 0.05–2 μg/band and 0.01–2 μg/band for OXY and FLU, respectively. The second developed and validated method is HPLC which is fulfilled on Hypersil BDS column-C18. A mobile phase of distilled water with 0.1%TFA/ acetonitrile in a ratio of 82: 18, v/v firstly then 70: 30, v/v after 9 min is used in a sequential isocratic elution at 210 nm for FLU and 267 nm for OXY, TRC, and CNA. Sensitive and wide linearity ranges are achieved at 0.05–200 μg/mL for both drugs. The two methods are applied successfully in cattle meat and milk for cited drugs determination. According to ICH guidelines, a validation study has been accomplished for the proposed methods. Statistical comparison has been carried out with official and reported methods. Eventually, the greenness of both procedures is evaluated using Eco-Scale which gives eco-friendly results. [ABSTRACT FROM AUTHOR]

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 aim of this research was to evaluate the physiological and behavioural parameters in Saanen goat kids treated with flunixin meglumine compared with no analgesic treatment after cautery disbudding using a device fueled by propane gas. At 7 days of age, 30 goat kids were randomly allocated to three groups: Sham (Sh) control, (i.e., simulating disbudding); Disbudding (Di), using thermal cauterization; Disbudding + Flunixin (DiFl), thermal cauterization + flunixin meglumine (2.2 mg/kg body weight, 15 min before treatment). Each kid was video-recorded for 30 min before and after treatment to evaluate the frequency of head shaking, head scratching, body shaking, grooming, head rubbing, jumping, running, and bleating. Blood samples were taken 30 min after disbudding to evaluate serum cortisol concentrations and white blood cell count. Heart rate (HR) and respiratory rate (RR) were measured using a stethoscope. Liveweight of goat kids was recorded at birth, -24 h and 7 days after treatment, and at 25 days of age. The mean frequency of head shaking and head scratching was higher (p = 0.0001) after disbudding in Di (37.5 ± 47.8 and 33.32 ± 31.2) group compared to Sh (3.42 ± 3.58 and 2.2 ± 1.8) and DiFl, (4.02 ± 2.76 and 4.42 ± 3.72) groups. The frequency of jumping was higher (p = 0.022) for Di (3.74 ± 2.24) than that of DiFl (0.39 ± 0.92). The remaining behaviours did not show differences (p > 0.05). HR and RR were higher (HR: p < 0.0048; RR: p < 0.035) in group Di (HR: 156 ± 13.6; RR: 66 ± 14.8) than in Sh (HR: 138 ± 8.48; RR: 55.6 ± 5.4) and in DiFl (HR: 136 ± 6.38; RR: 52.8 ± 4.13). No differences were detected between live weight, serum cortisol and white blood cell count data (p > 0.05). Results show that flunixin meglumine was effective at reducing pain-related behaviours when given at the time of disbudding. [ABSTRACT FROM AUTHOR]

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]

Donkeys are in the Equidae family but have several differences from horses. There are many studies on the pathophysiology of pain and its clinical signs in horses, but data are limited for donkeys. Therefore, the present study aimed to investigate biochemical effects of flunixin meglumine in donkeys subjected to pain induced by bloodless and surgical castration. Twenty healthy male donkeys were randomly divided into four groups: 1- Surgical castration with flunixin injection, 2- Surgical castration without flunixin injection, 3- Non-surgical castration with flunixin injection, and 4- Non-surgical castration without flunixin injection. Blood samples were collected a day before surgical procedures; four hours, one day, and two days after castration. Serum levels of IL-6, TNF-α, CRP, fibrinogen, cortisol, triglyceride, and cholesterol significantly increased in non-surgical castrated group compared to the other groups. Moreover, the levels of the measured parameters were significantly higher in the non-surgically castrated group compared to the surgically castrated group. Furtheremore, flunixin meglumine administration reduced the levels of the mentioned parameters, and it was significant for TNF-α and fibrinogen in the surgically castrated donkeys. However, in the nonsurgically castrated animals, there was a significant reduction in the levels of all mentioned parameters except for fibrinogen. It was concluded that non-surgical method, compared to the surgical method, was accompanied by more inflammation, stress, and pain; therefore, the surgical method could be suggested as a preferred technique for the castration of donkeys. Furthermore, the injection of flunixin meglumine could be suggested in the castration of donkeys, particularly in the bloodless technique., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

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]

This study aimed to evaluate the possible protective actions of chrysin and flunixine meglumine on testicular and spermatological injuries experimentally stimulated by copper. We separated 36 male Sprague-- Dawley rats into six equal groups: control, chrysin, flunixine meglumine, copper, copper +chrysin and copper +flunixine meglumine. Chrysin (50 mg/kg/bw/po), flunixine meglumine (2.2 mg/kg/bw/ip) and copper (500 mg/kg/bw/po) were administered day to day for 21 days. Copper administration caused significant morphological, physiological and biochemical alterations compared to the control group, which are as follows: production of oxidative stress, thanks to rise in testis lipid peroxidation and fall in antioxidant enzyme concentrations, decrease in sperm quality and increase in morphologic sperm abnormalities, suppression of spermatogenesis and prominent alterations in the testis histomorphology and induction of apoptosis in the testis tissues. On the other hand, compared to the copper group, treatment with chrysin or flunixine meglumine significantly attenuated these alterations. In conclusion, chrysin and flunixine meglumine have benefits such as antioxidant, antiapoptotic and anti- inflammatory against copper- induced testicular and spermatological damages in rats via the modulation of oxidative stress and apoptosis. Consequently, chrysin is a natural product which has comparable therapeutic actions to flunixine meglumine on the male reproductive system. [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.

Contents: This study aimed to determine the effect of flunixin meglumine treatment during and after the transfer of in vivo produced embryos to Angus (cows) and Holstein (cows and heifers) breeds of cattle on pregnancy rate. Holstein cows were used as donors in the study. A double dose of prostaglandin F2α was administered to the recipient animals for synchronization. Uterine flushing was performed in donors on day 7 after artificial insemination. A total of 295 transferable embryos were obtained. These embryos were transferred to Angus cows (n = 85), Holstein heifers (n = 80) and Holstein cows (n = 130). After the transfer, these animals were divided into three subgroups. The first subgroup (TI) was administered flunixin meglumine during embryo transfer, and the second subgroup (TII) was administered flunixin meglumine both during embryo transfer and on days 8 and 9 after the transfer. The third subgroup (TIII) was not administered anything and it was considered the control group. Pregnancy examination of the recipients was performed on days 30–35 after the transfer using real‐time ultrasonography. The pregnancy rates after embryo transfer were found to be 43.52% in Angus cows, 42.5% in Holstein heifers, and 24.61% in Holstein cows (p <.05). When the animals were not classified according to breed, the pregnancy rates in subgroups TI, TII and TIII were found to be 29.29%, 45.10% and 29.79%, respectively (p <.05). In addition, the pregnancy rates were higher in TII and TIII subgroups of Angus cows and Holstein heifers compared to that of Holstein cows (p <.05). As a result, the pregnancy rates obtained after embryo transfer in Angus cows and Holstein heifers were found to be higher than that in Holstein cows. In addition, it was concluded that the administration of flunixin meglumine during and during/after embryo transfer has a positive effect on pregnancy rates in Angus cows and Holstein heifers. [ABSTRACT FROM AUTHOR]

Flunixin meglumine is a highly efficacious nonsteroidal anti‐inflammatory drug commonly used in equine medicine and especially in performance horses. Recently, a new transdermal flunixin meglumine product has been approved for use in cattle. Although not currently approved for use in the horse, the convenience of this product may prove appealing for use in horses, warranting study. Six horses were administered a single transdermal dose of 500 mg and blood and urine samples collected for up to 96 h post‐administration. Serum for determination of thromboxane concentrations and whole blood samples was collected at various time and challenged with lipopolysaccharide, calcium ionophore, or methanol to induce ex vivo synthesis of eicosanoids. Concentrations of flunixin, 5‐OH flunixin, and eicosanoids were measured using LC‐MS/MS and non‐compartmental pharmacokinetic analysis performed on concentration data. Serum concentrations of flunixin and 5‐OH flunixin were above the limit of quantitation at 96 h post‐administration in both serum and urine. The mean (range) for Cmax, Tmax and the terminal half‐life were 515.6 (369.7–714.0) ng/ml, 8.67 (8.0 12.0) h, and 22.4 (18.3–42.5) h, respectively. Following transdermal administration, based on effects on eicosanoid synthesis, flunixin meglumine inhibited cyclooxygenase 1 and 2 and 15‐lipooxygenase activity, with anti‐inflammatory effects lasting for 24–72 h. [ABSTRACT FROM AUTHOR]

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) and phenylbutazone (PBZ) are potent anti‐inflammatory agents and as such their potential to mask injuries that would otherwise keep a horse from training or racing is concerning. A common practice in racetrack medicine in the USA is to administer the two drugs within close proximity (24 hours apart) of each other, raising the concern of pharmacokinetic interactions and enhanced anti‐inflammatory effects. Objectives: Describe the pharmacokinetics and effects of PBZ on the clearance of FM when administered in close proximity as well as effects on inflammatory mediators. Study design: Two‐way randomised balanced crossover experiment. Methods: Twelve Thoroughbred exercised horses received 500 mg FM IV alone or in combination with 2 g of IV PBZ 24 hours later. Blood and urine samples were collected prior to and for up to 120 hours post‐drug administration. Whole blood samples were collected at various times and challenged with lipopolysaccharide or calcium ionophore to induce ex vivo synthesis of eicosanoids. Concentrations of FM, PBZ and eicosanoids were measured using LC‐MS/MS and noncompartmental pharmacokinetic analysis performed on concentration data. Results: Flunixin meglumine clearance was significantly increased when horses received PBZ 24 hours post‐administration (P =.03). No other differences in pharmacokinetic parameters were noted between groups. Thromboxane B2 was significantly suppressed, relative to baseline for 96 hours post‐FM administration. Subsequent administration of PBZ prolonged the suppression. Prostaglandin E2 was decreased for 24 hours following administration of FM with subsequent administration of PBZ prolonging the suppression until 120 hours. PGF2alpha concentrations were decreased for up to 168 hours post‐FM administration. FM administration significantly decreased 15‐HETE. Main limitations: Small sample size and lack of a phenylbutazone‐only treatment group. Conclusions: Administration of PBZ post‐FM administration increased FM clearance. The anti‐inflammatory effects of FM appear to be prolonged when PBZ is administered 24 hours post‐administration. [ABSTRACT FROM AUTHOR]

The current investigation aims to evaluate the effects of flunixin meglumine (FM) and aspirin as non-steroid anti-inflammatory drug (NSAID) administration on estrous cycles characteristics and conception rate of Egyptian Baladi cows during hot season. In the first phase, 30 cows were divided into 3 groups, 10 cows for each treatment. The first group was treated with FM at the rate of 1.1 mg/kg body weight (BW) intramuscular, while the second group was administrated aspirin solution orally at the rate of 50 mg/kg BW. The third group was assigned as control (CG) that has no treatment. The FM group was administrated on day 14 after mating, while aspirin was given on day 14 and day 15 post-mating. All cows were mated naturally after showing estrus signs. Pregnancy diagnosis was carried 60 days after mating by rectal palpation. In the second phase, cows were monitored for estrus behavior by visual observation twice a day. The length of normal estrous cycles was 20, 23, and 22 days in cows treated with FM, aspirin, and control cows, respectively. There was no significant effect of treatment on the length of normal estrous cycles in Egyptian cows (P < 0.05). Proportions of long cycles in Egyptian cows that treated with FM or aspirin and control were 75, 67.7, and 57.1%, respectively. Short cycles were completely absent in cows that treated with FM or aspirin, but it was 29% in CG. Mounting behavior and tail rising were not detected in CG compared to 0 and 33% in FM or 25 and 33% in aspirin treated cows, respectively. Conception or pregnancy rate were 60, 40, and 30%, respectively, in FM, aspirin treated, and CG. Treatment cows whether FM or aspirin group did not influence (P < 0.05) progesterone concentration during the 14 days and 21 days from estrous cycle in pregnant and non-pregnant Egyptian Baladi cows than CG. In conclusion, the results of this study clearly indicated beneficial effect of FM and aspirin administration on intense of displayed estrous behavior and conception rate of Egyptian Baladi cows during the hot season. [ABSTRACT FROM AUTHOR]

The current clinical case was reported from Wayanad district of Kerala. The animal was a nine-year-old female chestnut pony weighing about 90 kg. Clinical signs observed were recumbency, anorexia, dehydration, rolling, kicking at the abdomen, tachycardia, abdominal distension, tympanic sounds on abdominal percussion, and frequent attempts to urinate and defecate. Treatment by using Flunixin meglumine at a dose rate of 1.1 mg/kg bodyweight Ringer's lactate, dextrose normal saline intravenously, ranitidine intramuscularly at a dose rate of 2 mg/kg bodyweight along with nasogastric intubation and coconut oil infusions successfully controlled the signs of colic and the animal recovered uneventfully. [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]

In this study, the pharmacokinetics of moxifloxacin (5 mg/kg) was determined following a single intravenous administration of moxifloxacin alone and co‐administration with diclofenac (2.5 mg/kg) or flunixin meglumine (2.2 mg/kg) in sheep. Six healthy Akkaraman sheep (2 ± 0.3 years and 53.5 ± 5 kg of body weight) were used. A longitudinal design with a 15‐day washout period was used in three periods. In the first period, moxifloxacin was administered by an intravenous (IV) injection. In the second and third periods, moxifloxacin was co‐administered with IV administration of diclofenac and flunixin meglumine, respectively. The plasma concentration of moxifloxacin was assayed by high‐performance liquid chromatography. The pharmacokinetic parameters were calculated using a two‐compartment open pharmacokinetic model. Following IV administration of moxifloxacin alone, the mean elimination half‐life (t1/2β), total body clearance (ClT), volume of distribution at steady state (Vdss) and area under the curve (AUC) of moxifloxacin were 2.27 hr, 0.56 L h−1 kg−1, 1.66 L/kg and 8.91 hr*µg/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t1/2β and AUC of moxifloxacin, they significantly reduced the ClT and Vdss. These results suggest that anti‐inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics. [ABSTRACT FROM AUTHOR]

The pharmacokinetics of levofloxacin (4 mg/kg), administered both alone and in combination with tolfenamic acid (2 mg/kg) and flunixin meglumine (2.2 mg/kg), was established after intravenous administration in sheep. Plasma levofloxacin concentrations were assayed by high-performance liquid chromatography and analysed according to the two-compartment open model. Following the administration of levofloxacin alone, the mean distribution half-life, elimination half-life, total clearance, volume of distribution at steady state and area under the plasma concentration-time curve were 0.20 h, 1.82 h, 0.39 L/h/kg, 0.96 L/kg and 10.40 h x mg/mL, respectively. Tolfenamic acid and flunixin meglumine caused a slow elimination and increased plasma concentrations of levofloxacin in combination administration. Levofloxacin, with an alteration in the dosage regimen, can be used effectively with tolfenamic acid and flunixin meglumine for the therapy of infections and inflammatory conditions in sheep. [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]