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White willow bark (WWB) is commonly used in combination with other medicinal herbs and analgesics to alleviate inflammatory pain in disbudded calves under organic management, but there is no evidence to confirm an effect of WWB on inflammatory biomarkers in calves. The objective of this study was to determine whether WWB affects the inflammatory biomarker prostaglandin E2 (PGE2) in healthy dairy calves. A randomized crossover trial with 2 periods and 5 treatments was used for this experiment. A 7-d washout period was used to minimize carryover effects. The treatments were (1) 57.6 mg/kg oral WWB (low dose; L-WWB), (2) 115.1 mg/kg oral WWB (medium dose; M-WWB), (3) 230.3 mg/kg oral WWB (high dose; H-WWB), (4) 2.2 mg/kg i.v. flunixin meglumine (FM), or (5) no treatment (NT). Calves (n = 25) were randomly assigned to receive 1 of the 25 treatment sequences. Blood samples were collected at 1, 2, and 4 h after administration to determine PGE2 and salicylic acid plasma concentrations. The WWB had 2,171 μg/g (± 4.3% relative standard error) salicin (0.22%). On average, calves in the FM (721 ± 274 pg/mL) treatment had lower PGE2 than calves in all other treatments. Calves in the NT (2,606 ± 271 pg/mL), L-WWB (2,509 ± 276 pg/mL), M-WWB (2,343 ± 270 pg/mL), and H-WWB (3,039 ± 270 pg/mL) treatments had similar PGE2 averaged across sampling times. Calves in the L-WWB (23.4 ± 1.9 ng/mL), M-WWB (21.5 ± 1.9 ng/mL), and H-WWB (23.3 ± 1.9 ng/mL) treatments had similar maximum salicylic acid plasma concentrations. Results from this study indicate that the WWB doses used in this experiment were ineffective at achieving dose-dependent PGE2 and salicylic acid plasma concentration responses.

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.

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.

Eating and rumination variables were recorded using a pressure sensor integrated into the noseband of a halter in 60 cows with left displaced abomasum (LDA) before and after postoperative administration of flunixin meglumine (FM). Group 1 comprised 9 healthy control cows that were used to establish reference intervals. Group 2 included 60 cows with LDA that received one of the following three treatments: intravenous saline solution (2A, n=20), 1.1 mg/kg FM (2B, n=20) or 2.2 mg/kg FM (2C, n=20) once daily for 3 days after right-flank omentopexy. Median eating times on the day before surgery were 93 (2A), 80 (2B) and 114 (2C) min, which were below the reference interval (246 to 381 min). On the day after surgery, eating times had increased significantly to 201 (2A), 172 (2B) and 216 (2C) min, after which time they continued to increase. Eating and rumination times, numbers of regurgitated feed boluses per day and chewing cycles per bolus did not differ among treated groups. Postoperative administration of FM did not affect eating and rumination variables in this study, and normalisation of these variables was attributable to surgical correction of LDA.Die Fress- und Wiederkauparameter von 60 Kühen mit linksseitiger Labmagenverlagerung (LLV) wurden nach postoperativer Verabreichung von Flunixin meglumin (FM) mittels Drucksensors im Halfter untersucht. Die Gruppe 1 bestand aus 9 gesunden Kühen für die Normalbereichsermittlung. Die Gruppe 2 umfasste 60 LLV-Kühe, die nach Omentopexie 3mal in 24-stündigen Abständen mit NaCl (2A), 1.1 (2B) oder 2.2 mg FM/kg (2C) behandelt wurden. Bei den LLV-Kühen lag die Fressdauer (Medianwert) bei den 3 Gruppen am Tag 0 mit 93, 80 und 114 Min. unterhalb des Normalbereichs von 246 bis 381 Minuten. Bereits am Tag 1 nach der Operation war sie mit 201, 172 und 216 Min. signifikant länger und stieg danach weiter an. Die Werte der 3 Behandlungsgruppen unterschieden sich nicht signifikant. Ähnliche Ergebnisse wurden für Wiederkaudauer, Anzahl Wiederkauboli und Kauschläge pro Wiederkaubolus ermittelt. Die Verabreichung von FM beeinflusste die Fress- und Wiederkauparameter in der vorliegenden Untersuchung nicht. Vielmehr war für die rasche Normalisierung die Omentopexie entscheidend.Les variables d’alimentation et de rumination ont été enregistrées à l’aide d’un capteur de pression intégré à la muserolle d’un licol chez 60 vaches avec déplacement à gauche de la caillette (LDA) avant et après l’administration postopératoire de flunixine méglumine (FM). Le groupe 1 comprenait 9 vaches témoins en bonne santé qui ont été utilisées pour établir des intervalles de référence. Le groupe 2 comprenait 60 vaches avec LDA qui ont reçu l’un des trois traitements suivants : solution saline intraveineuse (2A, n=20), 1,1 mg/kg FM (2B, n=20) ou 2,2 mg/kg FM (2C, n= 20) une fois par jour pendant 3 jours après omentopexie par le flanc droit. La durée médiane des repas la veille de la chirurgie était de 93 (2A), 80 (2B) et 114 (2C) minutes, ce qui était inférieur à l’intervalle de référence (246 à 381 min). Le lendemain de la chirurgie, la durée des repas avait augmenté de manière significative à 201 (2A), 172 (2B) et 216 (2C) minutes, après quoi elle a continué à augmenter. Les temps de repas et de rumination, le nombre de bolus alimentaires régurgités par jour et les cycles de mastication par bolus ne différaient pas entre les groupes traités. L’administration postopératoire de FM n’a pas affecté les variables d’alimentation et de rumination dans cette étude et la normalisation de ces variables était attribuable à la correction chirurgicale de la LDA.Le variabili di alimentazione e ruminazione sono state registrate utilizzando un sensore di pressione integrato nella fascia nasale di una cavezza in 60 vacche con abomaso dislocato a sinistra (LDA) prima e dopo la somministrazione post-operatoria di flunixina meglumine (FM). Il gruppo 1 comprendeva 9 vacche di controllo sane che sono state utilizzate per stabilire gli intervalli di riferimento. Il gruppo 2 comprendeva 60 vacche con LDA che avevano ricevuto uno dei seguenti tre trattamenti: soluzione salina per via endovenosa (2A, n=20), 1,1 mg/kg FM (2B, n=20) o 2,2 mg/kg FM (2C, n=20) una volta al giorno per 3 giorni dopo l’omentopessi del fianco destro. I tempi mediani per mangiare il giorno prima dell’intervento erano di 93 (2A), 80 (2B) e 114 (2C) min, e risultavano inferiori dell’intervallo di riferimento (da 246 a 381 min). Il giorno dopo l’intervento, i tempi di alimentazione erano aumentati significativamente a 201 (2A), 172 (2B) e 216 (2C) min, dopo di che hanno continuato ad aumentare. I tempi di alimentazione e di ruminazione, il numero di boli di mangime rigurgitati al giorno e i cicli di masticazione per bolo non differivano tra i gruppi trattati. La somministrazione post-operatoria di FM non ha influenzato le variabili di alimentazione e ruminazione in questo studio, e la normalizzazione di queste variabili era attribuibile alla correzione chirurgica della LDA.

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.

Objective: To detail an easy approach to identify the changes that moxifloxacin and flunixin meglumine have caused in the dam of female rats.Design: Randomized controlled experimental study.Animals: This study was conducted on thirty-five female (170-200 gm) mature white rats (170-200 gm) and clinically intact, 20 mature male albino rats for the purpose of mating. Procedures: Once mating has occurred, this is considered the first day of pregnancy. Rats were randomly divided into seven groups 1) a control group 2) The moxifloxacin group 6 days 3) the moxifloxacin group 13 days 4) the flunixin meglumine group 6 days 5) the flunixin meglumine group 13 days 6) the moxifloxacin and flunixin meglumine mg group 6 days 7) the moxifloxacin and flunixin meglumine mg group on day 13. Rats were killed on the days specified for the sixth day and the thirteenth day. Blood and liver samples were collected for biochemical analysis of blood and tissue for pathological examination.Results: Moxifloxacin and flunixin meglumine and their combination have been shown to have some negative effects in mothers of rats, so we recommend that caution be exercised when using moxifloxacin and flunixin meglumine during pregnancy. It was found that the tested drugs had caused a significant decrease in superoxide dismutase and glutathione levels compared to the control group. The histopathological examination of mothers, who were given moxifloxacin and flunixin meglumine and their mixtures, showed variable alterations in kidney, liver and placenta. Conclusion and clinical relevance: From the above it is clear that moxifloxacin and flunixin meglumine and their combination have caused some negative effects for pregnant rats, so we recommend that you use caution when using moxifloxacin and flunixin meglumine during pregnancy.

Background: Flunixin meglumine is a non-steroidal anti-inflammatory drug used in the treatment of several conditions in veterinary medicine. Objective: The study was aimed to investigate the analgesic and anti-inflammatory effects of flunixin meglumine in chicks. Methods: The up and down method was used to assess the median lethal dose (LD50) and effective median analgesic dose (ED50) of flunixin meglumine administered intraperitoneally (i.p.) and orally (p.o.) in chicks. From the obtained values we determined the drug safety indices. Electric stimulation method was used to determination the dose-dependent analgesic effect of flunixin meglumine in chicks. Analgesic and anti-inflammatory effects were dignified via the formalin test. Results: The median lethal doses (LD50) of flunixin were 143.24mg/kg intraperitoneally and 170.77mg/kg orally. The effective median analgesic doses (ED50) of flunixin meglumine in chicks were 9.34 mg/kg and 11.75 mg/kg for intraperitoneally and orally respectively. The Therapeutic Index, Standard Safety Margin and Therapeutic Ratio of flunixin through intraperitoneal and oral route were (15.35 , 14.53), (0.15 , 0.14) and ( 5.11 , 4.84) respectively. The dose-dependent analgesic effect of flunixin meglumine at 9 mg/kg, 18 mg/kg ip and 12 mg/kg, 24 mg/kg p.o started at 15 min after treatment and lasted over 120 min of treatment. The analgesic effect peak of flunixin meglumine through intraperitoneal and oral routes was 30 minutes after treatment. In formalin test, flunixin meglumine caused a significant rise in the latency to lift right foot in comparison with the control value, along with a significant decline in foot lifting frequency. A substantial decrease in foot thickness compared to control value has been demonstrated by the anti-inflammatory effects of flunixin meglumine. Conclusion: These results shows that the flunixin has analgesic and anti-inflammatory effects and form the backbone for further pharmacological studies as well as the medication could be safely administered to chicken.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used in veterinary medicine. Additionally, interest regarding the anti-infammatory properties of phytochemicals has emerged in recent years. In the present study, we aim to investigate the in vitro effects of meloxicam, flunixin meglumine, and harpagoside on the respiratory burst of porcine polymorphonuclear neutrophils (PMNs). We observed that harpagoside was able to suppress the respiratory burst, similarly to flunixin meglumine. Conversely, meloxicam enhanced the PMNs response. However, these effects were only detected at concentrations higher than those achievable in plasma and tissues. The present study intends to offer insights into the role of these molecules on phagocytosis mechanisms in animals to complement what is already known regarding human PMNs.

Objective To describe the use of therapeutic plasma exchange (TPE) in the treatment of flunixin meglumine overdose in a cria. Case summary A 3-day-old alpaca cria was diagnosed with ureteral obstruction and agenesis resulting in severe bilateral hydronephrosis. During hospitalization, the cria inadvertently received a flunixin meglumine overdose of >65 mg/kg. Here, we report the use of lipid emulsion and TPE to mitigate flunixin meglumine toxicosis. TPE appeared to prevent any flunixin-induced kidney or gastrointestinal injury, even in a patient with congenital defects of the urinary tract. New information provided This is the first report of the use of TPE in a cria.

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.

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

OBJECTIVE To evaluate IM injection of oxytetracycline as an experimental model to induce pain and assess the analgesic efficacy of flunixin meglumine (FM) in dairy cows. ANIMALS 15 healthy nonlactating Jersey (n = 10) and Holstein (5) cows. PROCEDURES In the first of 2 experiments, 5 Jerseys were administered oxytetracycline (10 mg/kg, IM), divided between the right side of the neck and left hind limb. The left side of the neck and right hind limb received sham injections. Cows were also randomly assigned to receive FM (2.2 mg/kg, IV; n = 3) or an equal volume of saline (0.9% NaCl) solution (0.044 mL/kg, IV; control; 2) once daily for 5 days. The mechanical nociceptive threshold (MNT) was measured before oxytetracycline administration and at predetermined times after each injection of the assigned treatment. Experiment 2 was similar to experiment 1 except it involved 5 Jerseys and 5 Holsteins, oxytetracycline was injected only in a hind limb, and the assigned treatment was administered for 10 days. RESULTS For both experiments, mean MNT for the oxytetracycline injection site was consistently less than that for the sham injection site in the hind limbs, and mean MNT at the hind limb oxytetracycline injection site for FM-treated cows was greater than that for control cows beginning on day 3. CONCLUSIONS AND CLINICAL RELEVANCE IM injection of oxytetracycline in a hind limb reliably induced signs of pain in dairy cows and, with validation, might be useful as an experimental model for assessing pain mitigation strategies in cattle.

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.

OBJECTIVE To quantify acute immunologic and metabolic responses of beef heifers following topical administration of transdermal flunixin meglumine (TDFM) at various times relative to bovine herpesvirus 1 (BHV1) and Mannheimia haemolytica challenges. ANIMALS 32 beef heifers (mean body weight, 170 kg). PROCEDURES Heifers were assigned to 1 of 4 groups. Heifers in the control group did not receive TDFM, whereas 1 dose of TDFM (3.3 mg/kg) was topically applied to heifers of groups A, V, and B at −144, −72, and 0 hours. All heifers were inoculated with 1 × 108 plaque-forming units of BHV1 in each nostril at −72 hours and with 1.18 × 106 CFUs of M haemolytica intratracheally at 0 hours. Vaginal temperature was recorded and blood samples were collected for quantification of select immunologic and metabolic biomarkers at predetermined times from −144 to 360 hours. RESULTS Mean vaginal temperature was similar between group A and the control group. Mean vaginal temperatures for groups V and B were generally lower than that for the control group following BHV1 and M haemolytica challenges, respectively. Mean neutrophil oxidative burst capacity and L-selectin expression at 0 hours were significantly decreased for group V relative to the other groups. Other biomarkers did not differ among the groups at any time. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that topical administration of TDFM to beef cattle effectively alleviated pyrexia without adverse effects on acute immunologic or metabolic responses when TDFM was administered at the same time as, but not before, respiratory pathogen challenge.

Amaç: Bu çalışmada; aşım sezonunda östrüsleri senkronize edilen İvesi ırkı koyunlarda, aşım sonrası fluniksin meglumin uygulamasının dölverimi üzerine etkisi araştırıldı. Gereç ve Yöntem: Çalışma en az bir doğum yapmış olan, 2-4 yaşlı, aynı bakım ve besleme şartlarında barındırılan 100 baş İvesi ırkı koyun üzerinde yürütüldü. Bu amaçla koyunlara aşım sezonu içerisinde (Ağustos-Kasım) 30 mg fluorogesteron asetat içeren vaginal sünger, vagina içerisine yerleştirildi (0. gün). Uygulamanın 11. gününde 10 mg PGF2α kas içi uygulandı. Vaginal süngerler 12. günde çıkarıldı ve 400 İÜ PMSG kas içi yapıldı. Kas içi PMSG enjeksiyonunu takiben östrüs gösteren koyunlara, fertilitesi bilinen koçlarla grup aşım yöntemiyle doğal aşım yaptırıldı. Aşım yaptırılan koyunlar 2 eşit gruba ayrıldı. Deneme grubu koyunlara (n=50) aşım sonrası 9. ve 10. günde 1.1 mg/kg dozunda fluniksin meglumin kas içi uygulanırken; kontrol grubuna dahil edilen koyunlara (n=50) herhangi bir işlem yapılmadı. Koyunların gebelik muayeneleri aşım sonrası 50. günde real time ultrason ile transabdominal yolla yapıldı. Bulgular: Deneme grubunda gebe kalma oranı % 40.9; kontrol grubunda % 33.3 olarak elde edildi (p, 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 (SeptemberOctober). On the 11th days after insertion of sponge, 10 mg PGF2α 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

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.

An inhibitor of PGF2α biosynthesis (flunixin meglumine, FM) was used to study the role of endogenous PGF2α on the luteolytic effect of exogenous PGF2α in mares. A 2-h infusion of PGF2α at a constant rate (total dose, 0.1 mg) on Day 10 (ovulation = Day 0) was used to mimic the maximal concentrations of a spontaneous pulse of a PGF2α metabolite (PGFM). Treatment with FM (1.7 mg/kg) was done 1 h before and 5 h after the start of PGF2α infusion. In hourly blood samples beginning 1 h before the start of PGF2α infusion, progesterone decreased (P 0.05) similarly by 5 h in each of the PGF2α and PGF2α+FM groups but not in the controls (n = 5). In a study of spontaneous luteolysis, the same FM dose was given every 6 h from Day 13 until Day 17 or earlier if CL regression was indicated by an 80% decrease in luteal blood-flow signals. Blood was sampled for progesterone assay each day and 8 h of hourly blood sampling was done each day to characterize PGFM concentrations and pulses. Progesterone (P4) was lower (P 0.05) in controls than in an FM group (n = 7) by Day 15. Luteolysis (P4 1 ng/mL) ended on Days 14-19 in individual controls. In contrast, luteolysis did not end until after Day 20 in 4 of 7 FM-treated mares. In the three mares with completion of luteolysis before Day 20 in the FM group, the interval from beginning to end of luteolysis was longer (P 0.02) (4.5 ± 0.6 days) than in the controls (3.0 ± 0.4 days). During 8-h sessions of hourly blood sampling on Day 14, concentration of PGFM was significantly lower in the FM group for the minimal, mean, and maximal per session. Pulses of PGFM were identified by a CV methodology on each day in 7 of 7 and 3 of 7 mares in the controls and FM group, respectively. The four FM-treated mares without a CV-identified pulse were the four mares in which luteolysis did not occur before Day 20. In mares with detected pulses, PGFM was lower at each nadir and at the peak (86% lower) in the FM group than in controls, but the interval between nadirs or base of a pulse was not different between groups. Hypothesis 1 that endogenous PGF plays a role in the luteolytic effect of exogenous PGF2α was not supported. Hypothesis 2 that an inhibitor of PGF2α biosynthesis prevented or minimized the prominence of PGFM pulses and increased the frequency of persistent CL was supported.

Violative chemical residues in animal-derived food products affect food safety globally and have impact on the trade of international agricultural products. The Food Animal Residue Avoidance Databank program has been developing scientific tools to provide appropriate withdrawal interval (WDI) estimations after extralabel drug use in food animals for the past three decades. One of the tools is physiologically based pharmacokinetic (PBPK) modeling, which is a mechanistic-based approach that can be used to predict tissue residues and WDIs. However, PBPK models are complicated and difficult to use by non-modelers. Therefore, a user-friendly PBPK modeling framework is needed to move this field forward. Flunixin was one of the top five violative drug residues identified in the United States from 2010 to 2016. The objective of this study was to establish a web-based user-friendly framework for the development of new PBPK models for drugs administered to food animals. Specifically, a new PBPK model for both cattle and swine after administration of flunixin meglumine was developed. Population analysis using Monte Carlo simulations was incorporated into the model to predict WDIs following extralabel administration of flunixin meglumine. The population PBPK model was converted to a web-based interactive PBPK (iPBPK) framework to facilitate its application. This iPBPK framework serves as a proof-of-concept for further improvements in the future and it can be applied to develop new models for other drugs in other food animal species, thereby facilitating the application of PBPK modeling in WDI estimation and food safety assessment.

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.

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.

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

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. RESUMO O objetivo deste estudo foi avaliar os efeitos da administração de flunixina meglumina sobre as taxas de prenhez e características da fase lútea da receptora no momento da transferência de embriões em bovinos. No experimento 1, embriões produzidos in vitro foram transferidos para 184 fêmeas, divididas em grupos controle e tratado (tratados com 1,1mg/kg de flunixina meglumina). No experimento 2, 22 fêmeas foram divididas em grupo controle (n=7); grupo 2 (n=8; animais submetidos à manipulação do trato reprodutivo semelhante à transferência de embriões no sétimo dia pós-cio); e grupo 3 (n=7; fêmeas submetidas à manipulação e ao tratamento com 1,1mg/kg de flunixina meglumina). No experimento 1, não foi observada diferença nos grupos controle e tratado (40,2% e 44,6%, respectivamente) para as taxas de prenhez. No experimento 2, não houve diferença na extensão da fase lútea entre os grupos, entretanto os animais do grupo 2 apresentaram concentrações plasmáticas de progesterona mais baixas que o grupo controle e o grupo 3. Portanto, conclui-se que a administração de flunixina meglumina no momento da transferência de embriões inibiu a redução das concentrações plasmáticas de progesterona, no entanto não foi eficaz para aumentar as taxas de prenhez de receptoras em bovinos.

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.

Pain management should be utilized with castration to reduce physiological and behavioral changes. Transdermal application of drugs require less animal management and fewer labor risks, which can occur with oral administration or injections. The objective was to determine the effects of transdermal flunixin meglumine on meat goats’ behavior post-castration. Male goats (N = 18; mean body weight ± standard deviation: 26.4 ± 1.6 kg) were housed individually in pens and randomly assigned to 1 of 3 treatments: (1) castrated, dosed with transdermal flunixin meglumine; (2) castrated, dosed with transdermal placebo; and (3) sham castrated, dosed with transdermal flunixin meglumine. Body position, rumination, and head- pressing were observed for 1 h ± 10 minutes twice daily on days −1, 0, 1, 2, and 5 around castration. Each goat was observed once every 5-minutes (scan samples) and reported as percentage of observations. Accelerometers were used to measure standing, lying, and laterality (total time, bouts, and bout duration). A linear mixed model was conducted using GLIMMIX. Fixed effects of treatment, day relative to castration, and treatment*day relative to castration and random effect of date and goat nested within treatment were included. Treatment 1 goats (32.7 ± 2.8%) and treatment 2 goats (32.5 ± 2.8%) ruminated less than treatment 3 goats (47.4 ± 2.8%, P = 0.0012). Head pressing was greater on day of castration in treatment 2 goats (P < 0.001). Standing bout duration was greatest in treatment 2 goats on day 1 post-castration (P < 0.001). Lying bout duration was greatest in treatment 2 goats on day 1 post-castration compared to treatment 1 and treatment 3 goats(P < 0.001). Transdermal flunixin meglumine improved goats’ fluidity of movement post-castration and decreased head pressing, indicating a mitigation of pain behavior.

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.

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.

A regressao prematura do corpo luteo (RPCL) diminui a eficiencia de programas de multipla ovulacao e transferencia de embrioes (MOTE) em pequenos ruminantes. O objetivo deste estudo foi avaliar o efeito do Flunixin meglumine (FM) e da gonadotrofina corionica humana (hCG) na recuperacao embrionaria e taxa de gestacao em ovelhas superovuladas com FSG e eCG. O estudo foi dividido em duas partes. No Experimento 1 doze doadoras foram divididas em tres grupos: controle, FM (1.1mg FM/ kg, SID, desde o dia da inseminacao artificial ate o dia da coleta de embrioes) e hCG (1000UI hCG, 84 horas apos a retirada do implante de progesterona). O numero corpos luteos (CL) e o numero e qualidade dos embrioes recuperados foram analisados. No Experimento 2, trinta e quatro doadoras foram divididas em dois grupos: controle e FM. O numero de CL e de embrioes recuperados foram avaliados. Cinquenta e quatro embrioes de cada grupo do Experimento 2 foram implantados em ovelhas receptoras e a taxa de gestacao foi analisada. No Experimento 1, foi encontrado maior numero (P

This study is "aimed" to evaluate and compare the efficacy of flunixin meglumine (FM), firocoxib (FX), and meloxicam (MX) after castration of horses. Thirty horses were submitted to open castration and divided into three groups (n = 10) depending on the anti-inflammatory drug administered: group I (GI) (FM, 1.1 mg kg1, IV, once a day [SID], 5 days); group II (GII) (FX, 0.1 mg kg1, IV, SID, 5 days), and group III (GIII) (MX, 0.6 mg kg1, IV, SID, 5 days). Clinical, behavioral, and hematological parameters and the peritoneal fluid (PF) were evaluated before (day [D] 0) and 1, 2, 3, 5, and 7 days afterward. In the postoperative, scores of limb rigidity and prepuce edema of animals of GII and GIII were greater than those of GI. Tachycardia was observed in the horses of GII and GIII and hyperthermia in GIII. An increase in the number of leukocytes, neutrophils, and monocytes without exceeding the reference values and hyperfibrinogenemia was observed in the animals of GI (D7), GII (D1-D7), and GIII (D7). There was reduction in serum protein after castration, together with an increase of this in the PF of the animals of the three groups. The PF on D0 was straw yellow and limpid, became reddish and cloudy on D1, and then gradually moved toward its normal color on the ensuing days, but without returning to normal on D7 in any of the groups. The results showed that castration triggers significant clinical and laboratory changes and that FM, FX, and MX are equally effective in controlling pain and inflammation in horses after castration; however, FM was more advantageous.

WOS: 000512441400001, PubMed: 32043623, 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 (t(1/2 beta)), total body clearance (Cl-T), volume of distribution at steady state (V-dss) 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*mu g/ml, respectively. While diclofenac and flunixin meglumine significantly increased the t(1/2 beta) and AUC of moxifloxacin, they significantly reduced the Cl-T and V-dss. These results suggest that anti-inflammatory drugs could increase the therapeutic efficacy of moxifloxacin by altering its pharmacokinetics., Coordination of Scientific Research Projects, University of Selcuk, Turkey [17401058], The Coordination of Scientific Research Projects, University of Selcuk, Turkey, Grant/Award Number: 17401058

RESUMO A analgesia pós-operatória em bovinos, por vezes, é negligenciada, frequentemente por falta de métodos quantitativos para seu diagnóstico e dimensionamento. Os objetivos deste trabalho foram: avaliar a pedometria e o acompanhamento bioquímico no pós-operatório de bovinos Nelore com onfalopatias e comparar a eficiência anti-inflamatória e analgésica entre diferentes doses de flunixin meglumine e meloxicam nesses animais. Foram utilizados 24 bovinos; deste total, 18 animais foram submetidos a laparotomia para tratamento das onfalopatias e, posteriormente, divididos em três grupos de animais: G1, que recebeu 1,1mg/kg flunixin; G2, 2,2mg/kg flunixin; G3, 0,5mg/kg meloxicam. A via de eleição para os tratamentos foi a IM, uma vez ao dia, totalizando seis aplicações. Outros seis bovinos saudáveis compuseram o grupo controle (GC). As coletas do sangue total para mensuração do cortisol plasmático foram realizadas antes e depois da cirurgia, assim como a leitura do pedômetro e o exame clínico. As concentrações plasmáticas de cortisol diferiram apenas no M0, entre o GC e os grupos tratados. O flunixin meglumine em diferentes doses e o meloxicam foram equivalentes no tratamento da dor pós-operatória e no efeito anti-inflamatório em bovinos submetidos à laparotomia para tratamento das onfalopatias. ABSTRACT Postoperative analgesia in cattle is sometimes overlooked, frequently due to the lack of quantitative methods for diagnosis and measurement. The objectives of this study were: to analyze the pedometric and biochemistry alterations of postoperative period in Nelore bovines with umbilical diseases; compare the anti-inflammatory and analgesic efficiency between different doses of flunixin meglumine and meloxicam in the postoperative of umbilical diseases in these animals. Twenty four bovines were used. From this total, 18 animals were submitted to laparotomy for treatment of umbilical diseases and subsequently divided into three groups of animals: G1, which received 1.1mg/kg flunixin, G2 2.2mg/kg flunixin, G3 0.5mg/kg meloxicam. Six other healthy cattle were allocated to the control group (CG). Total blood samples for plasma cortisol clinical examination was performed on standardizer times. Plasma cortisol concentrations differed only in the M0 between GC and treated groups. Flunixin meglumine in different doses and meloxicam were equivalent in the treatment of postoperative pain and anti-inflammatory effect in cattle submitted to laparotomy for the treatment of umbilical diseases.

Made available in DSpace on 2018-12-11T17:36:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2018-03-01 During the equine embryo transfer (ET), manipulation of the recipients cervix can stimulate the release of prostaglandin F2α by the uterine environment. Nonsteroidal anti-inflammatory drugs such as flunixin meglumine (FM) are frequently used in order to prevent a potential luteolysis. However, despite the reduction of inflammatory reaction and release of prostaglandins, the benefits of FM in pregnancy rates (PRs) of mares submitted to ET are not conclusive, and there is no information about the early pregnancy loss (EPL) rate after FM injection. The objective of this study was to evaluate the effect of FM in the PR and EPL in embryo-recipient mares. The data from 409 ET from a commercial breeding center were used, which 179 mares formed the control group (CG) and 230 recipients received the treatment of FM 1.1 mg/kg immediately after ET. There was no difference (P >.05) in PRs at 15 days (70.95% in the CG and 75.22% in treated mares) and 60 days (65.92% in CG and 65.22% in FM treated mares). However, there was a trend in the increase of early the pregnancy loss rate in mares that received FM (P =.0852). From the results of the present experiment, FM does not improve the PR in embryo-recipient mares. São Paulo State University—UNESP Santo Amaro University—UNISA Severino Sombra University—USS Vassouras São Paulo State University—UNESP

The objective of this study was to determine the effect of post AI administration of exogenous progesterone (P4) or a prostaglandin F2α (PGF2α) synthesis inhibitor agent on serum P4 concentrations and pregnancy per AI (P/AI) in lactating dairy cows. Eighty lactating cows were randomly allocated to one of four treatment groups: 1) CON (control), received 5 mL of saline solution on d 6 and 14 post AI; 2) IP4 (injection of P 4), received 125 mg of P4 im on d 6 and 14 post AI; 3) CIDR, received a controlled internal drug release insert containing 1.38g of P4 from d 6 to 20 post AI; and 4) FM (Flunixin Meglumine), received 0.625 g of Flunixin Meglumine, a nonsteroidal anti-inflammatory drug, twice daily on d 15 and 19 post AI. Blood samples were taken on d 0, 6, 14, 17 and 20 post AI to determine P4 concentrations. Transrectal palpation was performed between 40 and 45 d post AI to determine pregnancy status. All treatment groups (i.e. IP4, CIDR and FM) resulted in greater serum P4 concentration on d 17 and 20 post AI compared to CON (P < 0.05). Cows given a CIDR insert had greater concentrations of P 4 on d 17 and 20 than IP4 and FM cows (P < 0.05). However, no significant difference was found between IP4 and FM groups for serum P4 concentrations. The P/AI was greater (P < 0.05) in CIDR-treated cows (55%, 11/20) than CON (25%, 5/20), and intermediate in IP4 (40%, 8/20) and FM (35%, 7/20) cows. In summary, treatment with exogenous P4 (i.e. CIDR and IP4) or FM increased serum P4 concentrations in lactating dairy cows. However, results suggest that only CIDR administration would improve P/AI.

Simple Summary Postfracture treatment with nonsteroidal anti-inflammatory drugs might result in delayed healing. This study was aimed to evaluate and compare the effects of flunixin meglumine (FM) and ketoprofen on bone fracture healing in rabbits. A simple unilateral diaphyseal fracture was made and followed by fixation by K-wire. Healing was evaluated with radiography, histopathology, and immunohistochemistry. Interestingly, the results revealed that FM enhanced bone fracture healing combined with the activation of early collagen deposition, marked angiogenesis, and enhanced vascular endothelial growth factor. However, ketoprofen delayed bone fracture healing. These findings provide novel baseline information about the potential beneficial effects of FM on bone fracture healing cases. Abstract 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.

Testicular degeneration is a multifactorial process increasing the concentration of prostaglandins in seminal plasma. Both increase and decrease of these hormones tend to promote loss of seminal quality. Flunixin meglumine is a potent anti-inflammatory drug capable of modulating the production of prostaglandins and is widely used in female reproduction. However, it is rarely used in males with the same objective. Therefore, this study aimed to evaluate the effects of this drug on seminal quality of male lambs and goats with spermatic characteristics unfavorable for reproduction. To this end, a total of 15 breeding animals were evaluated, of which six goats and four sheep with poor seminal quality were selected according to the criteria established by the Brazilian College of Animal Reproduction (CBRA). Three semen samples were collected from each animal. Then, the flunixin meglumine treatment was initiated and ejaculates were collected at two different periods after the drug was administered (from day 21 until day 35 and from day 49 to day 63). Macroscopic and microscopic parameters were assessed in semen samples and scrotal circumference and percentages of sperm pathologies were measured and compared between the three periods. Data with normal distribution were analyzed using ANOVA at 5% probability, and comparisons between periods within the same species were performed using the Tukey test. An improvement was observed in the analyses of mass motility, percentage motility, and sperm vigor. Scrotal circumference had no variation. Concerning sperm pathologies, an increase in the number of normal spermatozoids was observed due to a significant reduction in minor and major defects, and the latter remained low even after the treatment was finished. Therefore, flunixin meglumine presented beneficial effects on seminal parameters of male goats and lamb with unfavorable spermatic characteristics. These findings indicate this drug may be used in the treating of males with testicular injuries or of breeders with reduced seminal quality due to advanced age.

This work was conducted to evaluate the effect of season of calving, parity and treatment with Flunixin Meglumine (NSAID) on conception rate in repeat breeder Egyptian Baladi cows and their crosses (Baladi x Friesian). Season of calving was divided into two season cold season (from November to April) and hot season (May to October). A total of 120 cows (n= 60 Baladi cows, n= 60 crossbred cows) were used in the study. 30 Baladi cows were taken and another crossbred was calved during the cold season and was divided into four groups of each group consisting of 15 cows. A total of 30 Baladi cows were also taken and another crossbred was calved during the hot season. It was divided into four groups, each consisting of 15 cows. Fifteen Baladi cows and another crossbred Flunixin Meglumine were treated (1.1 mg / kg BW intramuscular) at fourteenth day from mating in both cold and hot seasons and the other group was as control. The main results showed that the overall average conception rate in Baladi cows was 43.3% higher than that of crossbred cows (30%). Conception rate was higher in Baladi cows calved during the cold season (46.7%) than in cows calved during the hot season (40%). Conception rate of crossbred cows calved during the season was 33.3% higher than those born during the hot season (26.7%). Conception rate in cows in the fourth parity was higher in both Baladi and crossbred cows (83.3 and 50%) respectively compared to the second and third parity. Administration with Flunixin Meglumine resulted in an increase in conception rate of 13.3% in both Baladi and crossbred cows. Concentration of P4 was higher during the first three weeks of conception in the treated Flunixin Meglumine cows than in non-treated cows in both Baladi and crossbred cows. The current study showed the negative effect of the hot season on the rate of conception in cows raised under the conditions of the hot zones, as well as the positive effect of treatment with Flunixin Meglumine on the conception rate in cows. Conception rate was higher during the 4th parity in Baladi and their crosses. The current study recommends the synchronization of estrous in cows to arrange the births to be during the cold season to avoid the problems of the hot season, especially in southern Egypt, as well as treated with Flunixin Meglumine on the fourteenth day of mating in cows. Future studies on the treatment of Flunixin Meglumine in cows.

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.

The objective of this study was to evaluate the analgesic properties of transdermal flunixin meglumine when given at the time of dehorning on pain biomarkers. Twenty-four weaned male Holstein calves, 6 to 8 wk of age were enrolled into the study. The calves were randomly assigned to 1 of 3 treatment groups: 1) transdermal flunixin and dehorn (DH-FLU); 2) transdermal flunixin and sham dehorn (SHAM-FLU); and 3) placebo and dehorn (DH-PLBO). Transdermal flunixin at a label dose of 3.33 mg/kg (or placebo at an equivalent volume) was administered as a pour-on along the top-line of the calves in each treatment group concurrently with electrocautery dehorning or sham dehorning. Biomarker parameters collected and analyzed included: infrared thermography (IRT), mechanical nociception threshold (MNT), plasma cortisol, and substance P (SP). There were no differences in maximal temperatures detected for the IRT measurements of the medial canthus of the eye for the DH groups. Mean control point MNT measurements at 48 h were 3.14 kgF, 3.46 kgF, and 1.43 kgF for the DH-FLU, Sham-FLU, and DH-PLBO groups, respectively (P = 0.0001). No other differences of MNT were detected between the dehorned groups for the other test sites and time points. Plasma cortisol reached peak concentration at 20 min postdehorning for the DH-FLU and DH-PLBO groups and 10 min for SHAM-FLU group. Peak plasma cortisol concentrations were 32.0 ng/mL, 12.7 ng/mL, and 28.8 ng/mL for the DH-FLU, SHAM-FLU, and DH-PLBO groups, respectively. Cortisol concentrations were lower for the DH-FLU group at 90 min postdehorning compared to the SHAM-FLU and DH-PLBO groups ( = 0.04). Area under the effect curve (AUEC) were similar for all groups ( = 0.93). No statistical differences in SP concentrations between groups were detected for any of the time points. In conclusion, transdermal flunixin meglumine given at the time of dehorning did not provide substantial analgesia based on the pain biomarkers investigated. Further investigation into its role as part of a multimodal analgesic plan is warranted.

Simple Summary Disbudding is a routine procedure performed in goat kids at an early age, especially the ones in the dairy industry. The procedure is mainly done to increase safety for other animals and workers in intensive dairy farms. Disbudding is a painful procedure that affects the welfare of the kids. Effective and practical pain mitigation strategies to reduce the suffering of goat kids due to disbudding have not yet been found. We studied two different pain mitigation strategies for this procedure and concluded that they were not entirely effective. Consumers are increasingly aware of animal farming practices, especially the ones that can lead to suffering and pain, such as disbudding. It is crucial that pain mitigation strategies as well as possible alternative solutions to disbudding continue to be investigated. Nowadays, most of the goat milk production in developed countries is done in intensive indoors production systems. In these systems, procedures such as disbudding are performed routinely. Disbudding is done in young goat kids and is a recognised as a painful procedure. Pain mitigation strategies have been extensively researched, but a method that is effective in mitigating pain as well as being safe and practical has not yet been found. In this paper we used three treatment groups: one control and two groups with pain mitigation strategies for cautery disbudding, one using local anaesthesia (lidocaine) and a second one using local anaesthesia (lidocaine) plus an analgesic (flunixin meglumine). The behaviour of twenty-seven goat kids was recorded for three hours after disbudding. Overall, the goat kids that received both pain mitigation treatments dedicated more time performing active and positive behaviours. Nevertheless, the incidence of behaviours related to pain and discomfort was not consistently reduced. Research is still needed to find a practical and effective pain mitigation strategy for disbudding. A solution to this challenge would improve animal welfare as well as address societal concerns linked to the suffering of farm animals. info:eu-repo/semantics/publishedVersion

Transdermal administration is an important method of pharmacologic drug therapy in amphibians, made possible by their unique skin physiology and permeability. Despite this, there are relatively few studies that investigate transdermal pharmacokinetics in amphibians. The objective of this study was to investigate the pharmacokinetics of transdermal flunixin meglumine applied topically to marine toads (Rhinella marina). Twenty-one adult marine toads were administered flunixin meglumine (3.3 mg/kg) topically on their dorsum and randomized (n = 7/group) to blood collection at two timepoints from the following: 1, 2, 4, 8, 12, and 24 hours (h), using a sparse sampling protocol. Plasma was analyzed by ultra-performance liquid chromatography-tandem mass spectrometry. Samples were analyzed individually and reported as a mean of the samples at each timepoint. The mean peak plasma concentration was 6.31 µg/ml, area under the curve was 29.37 μg-h/mL, and elimination half-life was 2.79 h. No adverse effects were noted in any animals. A subset of 12 animals were euthanized at serial timepoints and necropsied. Histopathology of skin and major organs revealed one minimal superficial lesion in a single toad potentially attributable to flunixin meglumine administration; otherwise, no other treatment-related lesions were observed in 11 of 12 toads. A single topical dose of transdermal flunixin meglumine was rapidly absorbed in marine toads in the current study, and peak plasma concentrations exceeded therapeutic ranges established in cattle with no significant pathologic findings.

Hyperthermia is a common, serious issue when capturing wildlife and has the potential to cause irreversible damage and death if severe, especially among cervids. During a disease surveillance program in white-tailed deer, 72 animals were chemically immobilized for sample collection. Most of the deer became hyperthermic (body temperatures >2°C above physiological norm) and of those, three became severely hyperthermic (>4.2+°C above physiological norm). Since the deer were sedated for regulatory purposes, reversal of the immobilant was not an option to restore natural thermoregulation. Rather, flunixin meglumine was administered to each animal in conjunction with cold water enemas and/or copious external application of water. Body temperatures rapidly cooled and stabilized within normal physiological ranges after the treatment. Once the samples were collected, each deer was returned to their pens and given the immobilizing agents’ antidotes. All deer survived and appeared healthy 30 days post-capture indicating the protocol used for hyperthermia treatment was effective.

There is very little published literature objectively measuring analgesics and influence of suture selection on pain in bovine surgery. The objective of this study was to determine the impact of intravenous flunixin meglumine and suture material selection on pain measures following ventral midline celiotomy., American Association of Bovine Practitioners Proceedings of the Annual Conference, 2019

Selection of drugs for use in South American Camelids (SAC) is difficult due to lack of approved products for use in these species. Drugs and drug dosages are selected from limited published data or extrapolated from other species. Administration of intravenous (IV) medications to SAC can be difficult due to challenges in restraint, limited venous access, and unique cervical anatomy. Pharmaceuticals administered routes other than IV are attractive for use in SAC. Flunixin meglumine is a non-steroidal anti-inflammatory drug used in many species for its antipyretic, analgesic, and anti-inflammatory properties. In cattle, flunixin meglumine is specifically labeled for IV administration. A new transdermal (TD) formulation of flunixin has been developed and approved for use in cattle. The topical nature and longer duration of action compared to IV flunixin make this product ideal for use in SAC. The purpose of this study was to determine the pharmacokinetic and pharmacodynamic properties of IV and TD flunixin meglumine in alpacas., American Association of Bovine Practitioners Proceedings of the Annual Conference, 2019

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 × µg/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.

The objective of this study was to determine the likelihood that swine treated with flunixin meglumine could contaminate their environment, which could cause untreated swine housed in the same pen to ingest or absorb enough drug to be detected in their urine. Currently, any detectable level of flunixin found in the urine of pigs exhibited at livestock shows in Texas can disqualify the exhibitor. We conducted 2 trials in this study. The first, a pilot trial, placed pigs in 2 pens, with each pen housing a pig that did not receive a drug and a treated pig that received 2.2 mg/kg of flunixin intramuscularly. This trial demonstrated that transfer of the drug from treated to untreated pigs housed in close proximity was possible. The second trial was conducted using 10 pens, with a treated and untreated pig in each pen. Each pig receiving treatment was randomly selected and administered 2.2 mg/kg of flunixin intramuscularly; then, urine and plasma were collected from all swine for 10 d. Flunixin was detected at or above the limit of detection of 0.1 ng/mL in the urine of all treated and untreated pigs throughout the 10-d trial. Treated pigs had higher urine levels of flunixin than their untreated pen mates for 4 d post-treatment (P < 0.0001), but there was no statistical difference between pen mates during the last 5 d of the trial, making it impossible to differentiate treated from untreated pigs.