mobic and flunixin

Approved analgesic compounds in cattle are not currently available in the United States due to the lack of validated pain assessment methods and marker residue depletion studies. In this study, we compared the pharmacokinetic parameters and effect of preemptive analgesics administered to calves subjected to dehorning with local anesthesia. Holstein steers were randomly assigned to receive one of the following treatments per os (PO) or intravenously (IV) (n = 8/group): meloxicam (1 mg/kg PO), gabapentin (15 mg/kg PO), meloxicam (1 mg/kg), and gabapentin (15 mg/kg) PO, flunixin (2.2 mg/kg IV), or a placebo. Plasma drug, haptoglobin, substance P (SP) concentrations, serum cortisol concentrations, ocular thermography, mechanical nociceptive threshold (MNT), and average daily gain (ADG) were evaluated. Data were analyzed using mixed-effects models and noncompartmental pharmacokinetic analysis. Meloxicam, gabapentin, and meloxicam with gabapentin at the present doses did not reduce cortisol concentrations. Analgesic-treated calves had significantly lower plasma SP concentrations and improved ADG compared with controls. Flunixin calves had reduced circulating cortisol compared with controls. Meloxicam-treated calves showed an increase in MNT at two horn bud sites compared with the other treatments. Analgesics improved ADG and reduced biomarkers of pain, but effects differed by compound and route of administration.

Topics: Amines; Anesthetics, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cattle Diseases; Clonixin; Cyclohexanecarboxylic Acids; Dairying; Gabapentin; gamma-Aminobutyric Acid; Horns; Male; Meloxicam; Pain Measurement; Pain, Postoperative; Thiazines; Thiazoles

To evaluate the analgesic efficacy of the NSAIDs flunixin and meloxicam administered locally to the scrotum before ring castration.. Randomised, controlled, prospective study.. Forty eight single born male Merino lambs.. Lambs, aged approximately 4 weeks, were allocated to four groups for castration. Groups were: sham control; castration + saline; castration + flunixin; castration + meloxicam. Drugs (5 mL) were administered subcutaneously around the circumference of the scrotum immediately before castration. Cortisol, rectal temperature, haematology and plasma haptoglobin were measured before and up to 48 hours after treatment. Behaviour recorded by video for 12 hours after treatment was classified as pain avoidance behaviours in the first hour and postural behaviours in three 4 hour intervals.. Ring castration (saline group) induced a bi-phasic increase in cortisol with peaks at 90 minutes and 24 hours but no significant changes in haematology, haptoglobin or rectal temperature. Pain avoidance behaviours were increased and teat seeking decreased. Normal lying and normal standing postures were decreased and abnormal ventral lying, statue standing, abnormal standing and total abnormal postures increased. Flunixin decreased cortisol at 90 minutes (60.3 versus 117.3 nmol L(-1) ) and cortisol AUC (0-6 hours), decreased elevated leg movement (2.5 versus 5.4 events) and sum of pain avoidance behaviours (8.5 versus 16.7 events), improved time spent in normal ventral lying and decreased abnormal ventral lying and total abnormal postures compared to saline treated lambs. In a similar contrast, meloxicam caused non-significant decreases in cortisol at 90 minutes, cortisol AUC (0-6 hours) and pain avoidance behaviours, and significantly improved the postural behaviours normal ventral lying (26.7 versus 15.4%) and normal standing (13.9 versus 7.5%), and reduced abnormal standing and total abnormal postures. Physiological and behavioural responses associated with ring castration for both NSAID treatment groups were generally greater than sham controls.. Locally administered NSAIDs provided partial analgesia for ring castration.

Topics: Analgesics; Animals; Behavior, Animal; Body Temperature; Clonixin; Drug Administration Schedule; Hydrocortisone; Male; Meloxicam; Orchiectomy; Pain; Sheep; Sheep Diseases; Thiazines; Thiazoles; Weight Gain

To determine the effect of meloxicam and flunixin meglumine on recovery of ischemia-injured equine jejunum.. 18 horses.. Horses received butorphanol tartrate; were treated IV with saline (0.9% NaCl) solution (SS; 12 mL; n = 6), flunixin meglumine (1.1 mg/kg; 6), or meloxicam (0.6 mg/kg; 6) 1 hour before ischemia was induced for 2 hours in a portion of jejunum; and were allowed to recover for 18 hours. Flunixin and SS treatments were repeated after 12 hours; all 3 treatments were administered immediately prior to euthanasia. Selected clinical variables, postoperative pain scores, and meloxicam pharmacokinetic data were evaluated. After euthanasia, assessment of epithelial barrier function, histologic evaluation, and western blot analysis of ischemia-injured and control jejunal mucosa samples from the 3 groups were performed.. Meloxicam- or flunixin-treated horses had improved postoperative pain scores and clinical variables, compared with SS-treated horses. Recovery of transepithelial barrier function in ischemia-injured jejunum was inhibited by flunixin but permitted similarly by meloxicam and SS treatments. Eighteen hours after cessation of ischemia, numbers of neutrophils in ischemia-injured tissue were higher in horses treated with meloxicam or flunixin than SS. Plasma meloxicam concentrations were similar to those reported previously, but clearance was slower. Changes in expression of proteins associated with inflammatory responses to ischemic injury and with different drug treatments occurred, suggesting cyclooxygenase-independent effects.. Although further assessment is needed, these data have suggested that IV administration of meloxicam may be a useful alternative to flunixin meglumine for postoperative treatment of horses with colic.

Topics: Animals; Clonixin; Cyclooxygenase Inhibitors; Horse Diseases; Horses; Intestinal Diseases; Ischemia; Jejunum; Meloxicam; Thiazines; Thiazoles

The efficacy of meloxicam in the treatment of sows with mastitis-metritis-agalactia syndrome was investigated in comparison with flunixin. Basic therapy comprised administration of an antibiotic and oxytocin. A total of 200 sows and litters were examined in a double-blind clinical study with observations up to 8 days after the first treatment. The primary parameter, the clinical index score on day 2, consisting of rectal temperature, feed intake, general demeanour, respiratory rate, vaginal discharge, degree of inflammation of mammary glands, milk flow and nursing behaviour, revealed a significant (P < or = 0.05) non-inferiority of meloxicam in comparison with flunixin implying equal efficacy of both drugs. No significant differences were noted in the distribution of clinical efficacy scores within both groups at each day of examination. The differences in litter weight and daily weight gain per piglet were not significant between the two test groups. The mortality rates until day 8 of the study were without significant difference between groups. In piglets of diseased litters, however, the mortality rate was 50% lower in the meloxicam group in comparison with the reference group, this difference reaching statistical significance (P < or = 0.05).

Topics: Animals; Animals, Suckling; Anti-Inflammatory Agents, Non-Steroidal; Clonixin; Double-Blind Method; Female; Germany; Injections, Intramuscular; Lactation Disorders; Mastitis; Meloxicam; Puerperal Disorders; Swine; Swine Diseases; Syndrome; Thiazines; Thiazoles; Treatment Outcome

This study assessed the efficacy of meloxicam, flunixin, and ketoprofen in piglets undergoing routine castration and tail-docking. Six-day-old male piglets (8/group) received one of five randomized treatments: intramuscular saline (SAL PROC), meloxicam (MEL; 0.4 mg/kg), flunixin (FLU; 2.2 mg/kg), ketoprofen (KETO; 3.0 mg/kg) or sham (SAL SHAM; saline injection, no processing). Two hours post-dose, piglets were castrated and tail-docked. Plasma cortisol, interstitial fluid (ISF) prostaglandin E2 (PGE2) and activity levels via Actical® monitoring were used to estimate pain. SAL SHAM and FLU exhibited lower cortisol concentrations than SAL PROC at the time of processing (p = 0.003 and p = 0.049, respectively), and all NSAIDs exhibited lower PGE2 than SAL PROC at 3.69 hours (MEL p = 0.050; FLU p = 0.043 and KETO p = 0.031). While not statistically significant, PGE2 was higher in SAL PROC piglets vs. other treatment groups at most time points. There was also a high degree of variability between piglets, especially for SAL PROC. Activity levels were significantly decreased at multiple time points in SAL PROC and MEL piglets following processing. However, FLU and KETO piglets had increased activity levels closer to that of the SAL SHAM group, suggesting that these NSAIDs are more effective than MEL in providing analgesia. These results demonstrate that management strategies including administration of intramuscular flunixin or ketoprofen to reduce pain associated with processing will likely improve piglet health and welfare in the United States.

Topics: Animal Husbandry; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Castration; Clonixin; Dinoprostone; Extracellular Fluid; Hydrocortisone; Ketoprofen; Male; Meloxicam; Pain; Pain Management; Swine; Tail

The objective of this study was to determine the renal clearance of flunixin and meloxicam in pigs and compare plasma and urine concentrations and tissue residues. Urine clearance is important for livestock show animals where urine is routinely tested for these drugs. Fourteen Yorkshire/Landrace cross pigs were housed in individual metabolism cages to facilitate urine collection. This is a unique feature of this study compared to other reports. Animals received either 2.2 mg/kg flunixin or 0.4 mg/kg meloxicam via intramuscular injection and samples analyzed by mass spectrometry. Pigs were euthanized when drugs were no longer detected in urine and liver and kidneys were collected to quantify residues.. Drug levels in urine reached peak concentrations between 4 and 8 h post-dose for both flunixin and meloxicam. Flunixin urine concentrations were higher than maximum levels in plasma. Urine concentrations for flunixin and meloxicam were last detected above the limit of quantification at 120 h and 48 h, respectively. The renal clearance of flunixin and meloxicam was 4.72 ± 2.98 mL/h/kg and 0.16 ± 0.04 mL/h/kg, respectively. Mean apparent elimination half-life in plasma was 5.00 ± 1.89 h and 3.22 ± 1.52 h for flunixin and meloxicam, respectively. Six of seven pigs had detectable liver concentrations of flunixin (range 0.0001-0.0012 µg/g) following negative urine samples at 96 and 168 h, however all samples at 168 h were below the FDA tolerance level (0.03 µg/g). Meloxicam was detected in a single liver sample (0.0054 µg/g) at 72 h but was below the EU MRL (0.065 µg/g).. These data suggest that pigs given a single intramuscular dose of meloxicam at 0.4 mg/kg or flunixin at 2.2 mg/kg are likely to have detectable levels of the parent drug in urine up to 2 days and 5 days, respectively, after the first dose, but unlikely to have tissue residues above the US FDA tolerance or EU MRL following negative urine testing. This information will assist veterinarians in the therapeutic use of these drugs prior to livestock shows and also inform livestock show authorities involved in testing for these substances.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Clonixin; Half-Life; Injections, Intramuscular; Kidney; Liver; Male; Meloxicam; Sus scrofa

Topics: Animals; Animals, Wild; Anti-Inflammatory Agents, Non-Steroidal; Asia; Clonixin; Diclofenac; Europe; Extinction, Biological; Food Chain; Government Regulation; Humans; Livestock; Meloxicam; Raptors; Thiazines; Thiazoles; Veterinary Drugs

The purpose of this study was to investigate the pharmacokinetics of intravenous flunixin (2.2 mg/kg b.w.), oral meloxicam (1mg/kg b.w.), oral gabapentin (15 mg/kg b.w.) alone or co-administrated with meloxicam as well as the effects of these compounds on prostaglandin E2 (PGE2) synthesis in calves subjected to surgical dehorning. Plasma samples collected up to 24h after drug administration were analyzed by liquid chromatography/mass spectrometry, whereas blood PGE2 levels were measured by immunoenzymatic assay. In plasma, the terminal half-live of flunixin, meloxicam and gabapentin were 6.0 h (range, 3.4-11.0 h), 16.7h (range, 13.7-21.3h) and 15.3h (range, 11-32.9h), respectively. The co-administration of single doses of gabapentin and meloxicam did not seem to affect the pharmacokinetic profile of the two drugs except for gabapentin that reached significantly (P<0.05) higher maximum serum concentration (Cmax) when co-administered with meloxicam, than when administered alone. At 5, 360 and 720 min after dehorning, a significant (P<0.01) decrease in PGE2 concentration was observed in flunixin-treated animals compared with control calves. Moreover, circulating log PGE2 concentrations were inversely proportional to log flunixin concentrations (R(2)=0.75; P<0.0001). None of the other drugs significantly affected blood PGE2 levels. Further assessment of oral meloxicam and gabapentin in established pain models is required to formulate science based analgesic recommendations to enhance animal well-being after dehorning.

Topics: Amines; Analgesics; Animals; Area Under Curve; Cattle; Clonixin; Cyclohexanecarboxylic Acids; Dinoprostone; Gabapentin; gamma-Aminobutyric Acid; Half-Life; Horns; Male; Meloxicam; Pain; Random Allocation; Statistics, Nonparametric; Thiazines; Thiazoles

In equine medicine, stem cell therapies for orthopaedic diseases are routinely accompanied by application of NSAIDs (non-steroidal anti-inflammatory drugs). Thus, it has to be analysed how NSAIDs actually affect the growth and differentiation potential of MSCs (mesenchymal stem cells) in vitro in order to predict the influence of NSAIDs such as phenylbutazone, meloxicam, celecoxib and flunixin on MSCs after grafting in vivo. The effects of NSAIDs were evaluated regarding cell viability and proliferation. Additionally, the multilineage differentiation capacity and cell migration was analysed. NSAIDs at lower concentrations (0.1-1 μM for celecoxib and meloxicam and 10-50 μM for flunixin) exert a positive effect on cell proliferation and migration, while at higher concentrations (10-200 μM for celecoxib and meloxicam and 100-1000 μM for flunixin and phenylbutazone), there is rather a negative influence. While there is hardly any influence on the adipogenic as well as on the chondrogenic MSC differentiation, the osteogenic differentiation potential, as demonstrated with the von Kossa staining, is significantly disturbed. Thus, it can be concluded that the effects of NSAIDs on MSCs are largely dependent on the concentrations used. Additionally, for some differentiation lineages, also the choice of NSAID is critical.

Topics: Aggrecans; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Marrow Cells; Celecoxib; Cell Differentiation; Cell Movement; Cell Proliferation; Clonixin; Collagen Type II; Core Binding Factor Alpha 1 Subunit; Female; Horses; Male; Meloxicam; Mesenchymal Stem Cells; Phenylbutazone; Pyrazoles; Sulfonamides; Thiazines; Thiazoles

Reference materials are helpful to evaluate the performance of laboratories as well as being useful for the quality control of analytical procedures. Certified reference materials and other reference materials containing non-steroidal anti-inflammatory drugs in milk are however, not available. Therefore, production and evaluation of in-house reference materials with incurred residues of 5-hydroxyflunixin (5OHFLU) and meloxicam (MEL) in cow milk has been performed. The milk was collected 12h after dosing from cows which received meloxicam (0.5 mgkg(-1) b.w., i.v., single dose) or flunixin meglumine (2.2 mgkg(-1) b.w., i.v. during three days). The concentrations of analytes were checked in the milk samples. The milk was diluted with milk free from NSAIDs residues, homogenised, put into sterile 20 mL vials, frozen and lyophilised. The vials were weighed before and after lyophilisation, in order to calculate the amount of water necessary for reconstitution, and were stored at a temperature of -20+/-2 degrees C. For the homogeneity study, 10 random samples were analysed in duplicate and the results were interpreted using Cochran's test, Horwitz standard deviation and the test for a sufficient homogeneity. The assigned values, calculated from the results of the homogeneity test were 54.3 microgkg(-1) for 5OHFLU and 46.4 microgkg(-1) for MEL. The samples were tested for their stability every 14 days for 2 months and after 9 months. It has been confirmed that an appropriate homogeneity and stability of the produced in-house reference material has been obtained.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Chromatography, High Pressure Liquid; Clonixin; Drug Residues; Drug Stability; Meloxicam; Milk; Quality Control; Reference Standards; Spectrophotometry, Ultraviolet; Thiazines; Thiazoles

We report on the inhibitory activity of the NSAIDs meloxicam, carprofen, phenylbutazone and flunixin, on blood cyclooxygenases in the horse using in vitro enzyme-linked assays. As expected, comparison of IC50 indicated that meloxicam and carprofen are more selective inhibitors of COX-2 than phenylbutazone and flunixin; meloxicam was the most advantageous for horses of four NSAIDs examined. However at IC80, phenylbutazone (+134.4%) and flunixin (+29.7%) had greater COX-2 selectivity than at IC50, and meloxicam (-41.2%) and carprofen (-12.9%) had lower COX-2 selectivity than at IC50. We therefore propose that the selectivity of NSAIDs should be assessed at the 80% as well as 50% inhibition level.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Clonixin; Cyclooxygenase Inhibitors; Dinoprostone; Female; Horses; In Vitro Techniques; Male; Meloxicam; Phenylbutazone; Thiazines; Thiazoles; Thromboxane B2

Information on the pharmacokinetics and pharmacodynamics of anti-inflammatory drugs in birds is scarce. Choice of drug and of dosage is usually empirical, since studies of anti-inflammatory drugs are lacking. In this study, three common veterinary non-steroidal anti-inflammatory drugs (NSAIDs) were administered intravenously to five different bird species. Sodium salicylate, flunixin and meloxicam were selected as anti-inflammatory drugs. These NSAIDs were administered intravenously to chickens (Gallus gallus), ostriches (Struthio camelus), ducks (Anas platyrhynchos), turkeys (Meleagris gallopavo) and pigeons (Columba livia). Plasma concentrations of the drugs were determined by validated high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. Most bird species exhibited rapid elimination of these drugs. Ostriches had the fastest elimination rate for all three NSAIDs, but there were some interesting species differences. Chickens had a half-life that was approximately 10-fold as long as the other bird species for flunixin. The half-life of chickens and pigeons was three-fold as long as the other bird species for meloxicam, and, for salicylic acid, the half-life in pigeons was at least three-five-fold longer than in the other bird species.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Birds; Chromatography, High Pressure Liquid; Clonixin; Half-Life; Injections, Intravenous; Meloxicam; Sodium Salicylate; Species Specificity; Thiazines; Thiazoles

Three nonsteroidal anti-inflammatory drugs (NSAIDs) [sodium salicylate, flunixin (FLU) and meloxicam (MEL)] were administered intravenously to broiler chickens. Plasma concentrations were determined by high-performance liquid chromatography methods and pharmacokinetic parameters were calculated. After intravenous administration of sodium salicylate (50 mg/kg), FLU (1.1 mg/kg) and MEL (0.5 mg/kg), these drugs were eliminated from plasma with a mean half-life of 04.04, 05.45 and 03.20 h, respectively. Apparent volumes of distribution (0.39, 0.08 and 0.12 L/kg, respectively) indicated that tissue distribution was limited for the three drugs. Total body clearance was 70 mL/h.kg for sodium salicylate and 10 and 25 mL/kg.h for FLU and MEL, respectively. Based on the pharmacokinetic parameters these NSAIDs may offer possibilities for treatment of various conditions in chickens.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Chickens; Chromatography, High Pressure Liquid; Clonixin; Half-Life; Injections, Intravenous; Meloxicam; Sodium Salicylate; Species Specificity; Thiazines; Thiazoles; Tissue Distribution