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American Journal of Veterinary Research Apr 2011To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa.
OBJECTIVE
To evaluate the effects of carprofen and meloxicam on conductance and permeability to mannitol and on the histologic appearance of sections of canine gastric mucosa.
SAMPLE
Gastric mucosa from 6 mature mixed-breed dogs.
PROCEDURES
Sections of gastric mucosa were mounted in Ussing chambers, and carprofen (40 or 400μg/mL [CAR40 and CAR400, respectively]), meloxicam (8 or 80μg/mL [MEL8 and MEL80, respectively]), or no drug (controls) was added to the bathing solution. For all sections, conductance was calculated every 15 minutes for 240 minutes and flux of mannitol was calculated for 3 consecutive 1-hour periods; histologic examination was performed after the experiment. The area under the conductance-time curve for each chamber was calculated. Values of conductance × time, flux of mannitol, and the frequency distribution of histologic findings were analyzed for treatment effects.
RESULTS
For CAR400- and MEL80-treated sections, conductance X time was significantly higher than that for control and MEL8-treated sections. The effect of CAR40 treatment was not different from that of any other treatment. Over the three 1-hour periods, mannitol flux increased significantly in MEL80-, CAR40-, and CAR400-treated sections but not in MEL8- treated or control sections. Major histologic changes including epithelial cell sloughing were limited to the CAR400-treated sections.
CONCLUSIONS AND CLINICAL RELEVANCE
In the gastric mucosa of dogs, carprofen and meloxicam increased in vitro conductance and permeability to mannitol. At a concentration of 400 μg/mL, carprofen caused sloughing of epithelial cells. Carprofen and meloxicam appear to compromise gastric mucosal integrity and barrier function in dogs.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Diuretics, Osmotic; Dogs; Gastric Mucosa; Mannitol; Meloxicam; Permeability; Thiazines; Thiazoles
PubMed: 21453160
DOI: 10.2460/ajvr.72.4.570 -
Iranian Journal of Basic Medical... Feb 2014Drug delivery through the skin can transfer therapeutic levels of drugs for pharmacological effects. Analgesics such as NSAIDs have gastrointestinal side effects and...
OBJECTIVE(S)
Drug delivery through the skin can transfer therapeutic levels of drugs for pharmacological effects. Analgesics such as NSAIDs have gastrointestinal side effects and topical dosage forms of these drugs are mainly preferred, especially for local pains. Meloxicam is one of NSAIDs with no topical form in the market. In this research, we attempted to quantify the skin permeation of a meloxicam topical preparation and to show how permeation would be increased by using thymol as an enhancer. The effect of eutectic point of drug and thymol mixture on rate and extent of skin permeation was also studied.
MATERIALS AND METHODS
Different mixtures of thymol and meloxicam (2:8, 4:6, 5:5, 6:4, 8:2) were prepared and their melting point were obtained by differential scanning calorimetry. Then drug permeation was measured using diffusion cells and the Guinea pig skin.
RESULTS
Mixtures in ratios 5:5 and 4:6 of meloxicam / thymol showed a new endotherm at 149 and 140°C in DSC thermograms. The permeability of meloxicam from the creams containing 6:4, 5:5 and 4:6 ratios of meloxicam to thymol were 4.71, 15.2, 22.06 µg/cm(2) respectively. This was significantly different from the cream of pure meloxicam (3.76 µg/cm(2)).
CONCLUSION
This study set out to determine that thymol plays as a skin permeation enhancer and increases the meloxicam skin absorption and this enhancement is significant at the eutectic point of drug-enhancer mixture.
PubMed: 24711894
DOI: No ID Found -
The Journal of Reproduction and... Aug 2022Ovulation is an inflammation-like process, and cyclooxygenase-2 (COX-2)-dependent production of prostaglandin E (PGE) is its key mediator. Balanced regulation of...
Ovulation is an inflammation-like process, and cyclooxygenase-2 (COX-2)-dependent production of prostaglandin E (PGE) is its key mediator. Balanced regulation of inflammatory processes in high-yielding dairy cows may be essential for physiological ovulation and fertility. This study aimed to elucidate the mechanisms underlying ovulation failure and cyst development after disturbing intrafollicular inflammatory cascades. Therefore, nonselective (indomethacin and flunixin-meglumine), COX-2 selective (meloxicam), and highly COX-2 selective (NS-398) inhibitors were injected into preovulatory follicles 16 h after administration of GnRH, and ovulation was monitored via ultrasound examination. Additionally, follicular fluid was collected after injection of indomethacin, meloxicam, and NS-398. Moreover, primary granulosa cell cultures from preovulatory follicles were prepared and treated with indomethacin, meloxicam, and NS-398. The concentrations of 17β-estradiol, progesterone, and prostaglandin E (PGE) in the follicular fluid and cell supernatant were estimated. Indomethacin and flunixin-meglumine blocked ovulation, even at low doses, and led to ovarian cyst development. The selective and highly selective COX-2 inhibitors meloxicam and NS-398 were not effective in blocking ovulation. However, indomethacin, meloxicam, and NS-398 significantly and comparably reduced PGE concentration in vivo and in vitro (P < 0.05) but had no effect on estradiol or progesterone production. This may contradict the generally accepted hypothesis that PGE is a key mediator of ovulation and progesterone production. Our results suggest a connection between ovarian disorders and inflammatory actions in early postpartum cows.
Topics: Animals; Cattle; Cyclooxygenase 2; Cyclooxygenase Inhibitors; Dinoprostone; Estradiol; Female; Indomethacin; Meglumine; Meloxicam; Ovarian Follicle; Ovulation; Progesterone
PubMed: 35527004
DOI: 10.1262/jrd.2021-148 -
Animal : An International Journal of... Mar 2012Farrowing is an intrinsically risky process for both the sow and the piglets that can cause welfare and economic problems. The effects of the non-steroidal... (Randomized Controlled Trial)
Randomized Controlled Trial
Farrowing is an intrinsically risky process for both the sow and the piglets that can cause welfare and economic problems. The effects of the non-steroidal anti-inflammatory drug meloxicam on post-farrowing behaviour of sows, and the performance of piglets were investigated. A total of 48 sows were randomly allocated at the day of farrowing (day 0) into two homogeneous groups regarding parity, and treated with either meloxicam or saline solution as placebo. For each sow, number of position changes, total time lying and standing or sitting, feed intake and rectal temperature (RT) were recorded during 3 days after farrowing. Piglets were individually weighed at farrowing and at weaning. The number of position changes did not show significant differences between treatments (P = 0.79). Sows spent significantly less time lying during day +3 after farrowing in the meloxicam group than in the placebo group (P = 0.04). Feed intake and RT showed a parity effect (P < 0.001 in both cases); however, no treatment effect was observed (P = 0.67 and P = 0.47, respectively). Pre-weaning mortality rate in piglets was not affected by treatment. In litters from multiparous sows, piglets of low birth weight (defined as percentile 15: BW <1180 g) had an average daily gain significantly higher in the meloxicam group than in the placebo group (196.6 ± 7.2 v. 166.6 ± 9.1 g/day; P = 0.03). Although the administration of meloxicam 90 min after farrowing showed a positive effect on the total time lying of the sows, additional investigations are required to better qualify relevant indicators of pain following farrowing in sows and to specify the analgesic effects of meloxicam on piglet performance.
Topics: Animal Husbandry; Animal Welfare; Animals; Anti-Inflammatory Agents, Non-Steroidal; Female; Inflammation; Meloxicam; Motor Activity; Pain; Parity; Parturition; Swine; Swine Diseases; Thiazines; Thiazoles
PubMed: 22436229
DOI: 10.1017/S1751731111001790 -
Journal of Veterinary Internal Medicine Jul 2020Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would...
BACKGROUND
Little information is available about endotoxemia in donkeys. Characterizing the systemic inflammatory response (SIRS) to lipopolysaccharide (LPS) in donkeys would provide valuable clinical and therapeutic information. The effects of meloxicam on endotoxemia have not been studied in this species.
OBJECTIVES
To study the pathophysiology and gene expression associated with experimentally induced endotoxemia, and evaluate the effects of meloxicam on experimentally induced endotoxemia in donkeys and in equine monocyte cultures.
ANIMALS
Six healthy adult female donkeys.
METHODS
Endotoxemia was induced by an IV infusion of LPS for 30 minutes. Animals either received 20 mL of saline or 0.6 mg/kg of meloxicam IV after LPS infusion. The experiments lasted 6 hours. Blood samples were collected serially for hematology, serum biochemistry, interleukin measurement, and leukocyte gene expression analysis. Vital signs were recorded throughout the study. Monocyte cultures were used to test the effects of meloxicam on LPS-activated monocytes.
RESULTS
Lipopolysaccharide induced fever, leukopenia, and neutropenia of similar magnitude in both groups, but meloxicam attenuated increases in plasma lactate, tumor necrosis factor-alpha (TNFα), and interleukin 1β concentrations compared to controls. No differences were detected between groups for cytokine mRNA expression. Furthermore, meloxicam decreased TNFα release in LPS-activated monocyte cultures.
CONCLUSIONS AND CLINICAL IMPORTANCE
Meloxicam could be a feasible option for the treatment of endotoxemia and SIRS in donkeys. Additional studies are necessary to investigate possible meloxicam-related posttranscriptional regulation and to compare this drug with other nonsteroidal anti-inflammatory drugs (NSAIDs) in animals with endotoxemia.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cells, Cultured; Endotoxemia; Equidae; Female; Interleukin-1beta; Lactic Acid; Lipopolysaccharides; Meloxicam; Monocytes; Systemic Inflammatory Response Syndrome; Tumor Necrosis Factor-alpha
PubMed: 32463537
DOI: 10.1111/jvim.15783 -
Journal of the American Veterinary... Jul 2021To determine the pharmacokinetics of meloxicam in Wyandotte hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1...
OBJECTIVE
To determine the pharmacokinetics of meloxicam in Wyandotte hens and duration and quantity of drug residues in their eggs following PO administration of a single dose (1 mg of meloxicam/kg [0.45 mg of meloxicam/lb]) and compare results with those previously published for White Leghorn hens.
ANIMALS
8 healthy adult Wyandotte hens.
PROCEDURES
Hens were administered 1 mg of meloxicam/kg, PO, once. A blood sample was collected immediately before and at intervals up to 48 hours after drug administration. The hens' eggs were collected for 3 weeks after drug administration. Samples of the hens' plasma and egg whites (albumen) and yolks were analyzed with high-performance liquid chromatography.
RESULTS
Mean ± SD terminal half-life, maximum concentration, and time to maximum concentration were 5.53 ± 1.37 hours, 6.25 ± 1.53 μg/mL, and 3.25 ± 2.12 hours, respectively. Mean ± SD number of days meloxicam was detected in egg whites and yolks after drug administration was 4.25 ± 2 days and 9.0 ± 1.5 days, respectively.
CONCLUSIONS AND CLINICAL RELEVANCE
Compared with White Leghorn hens, meloxicam in Wyandotte hens had a longer terminal half-life, greater area under the plasma concentration-versus-time curve from time 0 to infinity, a smaller elimination rate constant, and a longer mean residence time-versus-time curve from time 0 to infinity, and drug persisted longer in their egg yolks. Therefore, the oral dosing interval of meloxicam may be greater for Wyandotte hens. Results may aid veterinarians on appropriate dosing of meloxicam to Wyandotte hens and inform regulatory agencies on appropriate withdrawal times.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Chickens; Female; Half-Life; Meloxicam; Ovum; Thiazines; Thiazoles
PubMed: 34125605
DOI: 10.2460/javma.259.1.84 -
PloS One 2018To assess the effects of a topical anaesthetic (TA) and buccal meloxicam (BM) on behaviour, maximum wound temperature and wound morphology following amputation dehorning...
To assess the effects of a topical anaesthetic (TA) and buccal meloxicam (BM) on behaviour, maximum wound temperature and wound morphology following amputation dehorning of beef calves, 50 unweaned Hereford calves were randomly allocated to: (1) sham dehorning / control (CON, n = 14); (2) amputation dehorning (D, n = 12); (3) amputation dehorning with pre-operative buccal meloxicam (DBM, n = 12); and (4) amputation dehorning with post-operative topical anaesthetic (DTA, n = 12). Videos of the calves were captured for 3 h following treatment. Each calf was later observed for 5 min every hour and the frequency and duration of specific behaviours displayed during these focal periods was recorded. Infrared and digital photographs of dehorning wounds were collected from all dehorned calves on days 1, 3 and 7 following treatment. Infrared photographs were used to identify the maximum temperature within the wound area. Digital photographs were used to score wounds based on visual signs of inflammation and healing, using a numerical rating scale of 1 to 3, with morphological aspects of inflammation increasing and morphological aspects of healing decreasing with progressive scores. CON calves displayed fewer head shakes than all dehorned calves at 2 and 3 h following treatment (P = 0.025). CON and DTA calves displayed less head turns than DBM calves at 2 h following treatment (P = 0.036). CON calves displayed fewer combined point behaviours than all dehorned calves at 2 h following treatment (P = 0.037). All dehorning wounds had a greater maximum temperature on days 3 and 7 compared to day 1 (P = 0.003). All wound morphology scores decreased from day 1 to day 3 and wound morphology scores of DBM and DTA calves increased from day 3 to day 7 (P = 0.03). Although flystrike may have confounded these observations, no clear effects of TA or BM on behaviour, maximum wound temperature or wound morphology following dehorning of calves were observed. Further research is required to evaluate the analgesic efficacy of these products for amputation dehorning of calves.
Topics: Administration, Topical; Anesthetics, Local; Animals; Anti-Inflammatory Agents, Non-Steroidal; Behavior, Animal; Body Temperature; Cattle; Horns; Inflammation; Male; Meloxicam; Pain Management; Pain, Postoperative
PubMed: 29897950
DOI: 10.1371/journal.pone.0198808 -
Journal of the American Association For... Mar 2021The sustained-release formulation of meloxicam (MSR) is a compounded NSAID that may provide pain relief for as long as 72 h after administration. MSR injection-site skin...
The sustained-release formulation of meloxicam (MSR) is a compounded NSAID that may provide pain relief for as long as 72 h after administration. MSR injection-site skin reactions have occurred in several species but have not previously been observed in mice. We investigated the development and progression of localized skin reactions after a single injection of MSR in Crl:CD1(ICR), C57BL/6J, and BALB/cJ mice. Each mouse received a subcutaneous injection of MSR ( = 60), standard-formulation meloxicam (MEL; = 24) or saline (control; SC; = 24) and was scored daily according to a 5-point system for erythema and mass characteristics. Mice were euthanized at either 7 or 14 d after injection and underwent postmortem analysis. MSR-treated mice had more erythematous and mass reactions than did MEL and SC mice. Mass lesions developed in 49 MSR mice (82%; 95% CI, 70% to 90%), 5 MEL animals (21%; 95% CI, 7% to 42%), and 1 SC mouse. MSR-treated BALB/cJ developed erythematous lesions less frequently than similarly treated Crl:CD1(ICR) or C57BL/6J. Lesions often were ventrolateral to the injection site. The median times to the appearance of mass and erythematous lesions were 2 d and 3 d, respectively. Histologically, the erythematous and mass reactions correlated with necrotizing to pyogranulomatous injection-site panniculitis. Inflammation severity scores at 7 and 14 d after injection were greater in the MSR-treated group than the other 2 groups. No strain- or sex-associated differences emerged except that inflammation severity scores at day 14 were higher in Crl:CD1(ICR) females than males. The character of the inflammatory response in MSR-treated mice did not differ between 7 and 14 d after injection, indicating that MSR-induced inflammation is slow to resolve. The ventral migration and delayed onset of MSR injection-site reactions could result in their being attributed to another cause or not being identified. Researchers and clinicians should be aware of the potential for slowly resolving injection-site reactions with MSR.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Delayed-Action Preparations; Female; Injections, Subcutaneous; Male; Meloxicam; Mice; Mice, Inbred Strains; Sex Characteristics
PubMed: 33402233
DOI: 10.30802/AALAS-JAALAS-20-000042 -
Journal of Dairy Science Nov 2020During inflammation of the mammary gland, the blood-milk barrier, which is predominantly composed of mammary epithelial cells, loses its integrity and gradients between...
During inflammation of the mammary gland, the blood-milk barrier, which is predominantly composed of mammary epithelial cells, loses its integrity and gradients between blood and milk cannot be maintained. Nonsteroidal anti-inflammatory drugs (NSAID) are commonly used systemically in combination with local administration of antimicrobials in mastitis treatments of dairy cows to improve the well-being of the cow during the disease. However, the knowledge about their effects on the blood-milk barrier is low. This study aimed to investigate effects of different NSAID, with different selectivity of cyclooxygenase-inhibition, on the transepithelial electrical resistance (TEER) and capacitance, cell viability, and expression of tumor necrosis factor α of bovine mammary epithelial barriers in vitro. Primary mammary epithelial cells of 3 different cows were challenged with lipopolysaccharide (LPS) from Escherichia coli with or without addition of ketoprofen (1.25 mg/mL or 4 mM), flunixin meglumine (1.0 mg/mL or 4 mM), meloxicam (0.25 mg/mL, 0.75 mg/mL, or 4 mM), diclofenac (0.75 mg/mL or 4 mM) or celecoxib (0.05 mg/mL) for 6 h. Concentrations were adapted to comparable relations of the recommended dosage for systemic application. Additionally, a similar molar concentration of all NSAID was used. Lipopolysaccharide with or without NSAID induced a decrease in TEER within 5 h, which returned to control level within 14 h. Viability of cells challenged with LPS only was not affected. However, the cell viability was decreased with increasing concentrations of NSAID and this effect was amplified with simultaneous LPS challenge. Ketoprofen at both dosages, flunixin meglumine at 1.0 mg/mL, and meloxicam at 0.75 mg/mL accelerated the recovery of TEER in comparison to LPS only (return to control level within 9 h). The comparison of NSAID effects at the same molecular quantity of 4 mM showed different effect on the barrier in which ketoprofen accelerated the recovery after LPS-induced barrier opening, whereas meloxicam and diclofenac slowed down the recovery (return to control level after 24 h). In conclusion, NSAID do not prevent the mammary epithelial barrier opening by LPS; however, ketoprofen, flunixin meglumine, and meloxicam obviously support the re-establishment of the barrier integrity. Used in mastitis therapy at an optimized dosage the tested NSAID would likely support the recovery of milk composition. However, an overdose of NSAID would likely cause tissue irritation and in turn, a delayed recovery of the barrier permeability.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cattle; Cell Count; Clonixin; Cyclooxygenase Inhibitors; Epithelial Cells; Escherichia coli; Female; Inflammation; Ketoprofen; Lipopolysaccharides; Mammary Glands, Animal; Mastitis, Bovine; Meloxicam; Milk; Tumor Necrosis Factor-alpha
PubMed: 32896404
DOI: 10.3168/jds.2020-18818 -
American Journal of Veterinary Research May 2013To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep. (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To determine the pharmacokinetics of meloxicam after IV and PO administration to 6 healthy sheep.
ANIMALS
6 healthy adult Dorset cross sheep (5 males and 1 female).
PROCEDURES
Meloxicam (0.5 mg/kg, IV, or 1.0 mg/kg, PO) was administered in a randomized crossover design with a 10-day washout period. Blood samples were collected at predetermined times over 96 hours. Serum drug concentrations were determined by high-pressure liquid chromatography with mass spectrometry. Computer software was used to estimate values of pharmacokinetic parameters through noncompartmental methods.
RESULTS
Following IV administration (n = 5), the geometric mean (range) elimination half-life was 14.0 hours (10.5 to 17.0 hours), volume of distribution was 0.204 L/kg (0.171 to 0.272 L/kg), and clearance was 0.17 mL/min/kg (0.12 to 0.27 mL/min/kg). Following oral administration (n = 6), maximum serum concentration was 1.72 μg/mL (1.45 to 1.93 μg/mL), time to maximum serum concentration was 19.0 hours (12.0 to 24.0 hours), clearance per bioavailability was 0.22 mL/min/kg (0.16 to 0.30 mL/min/kg), and terminal half-life was 15.4 hours (13.2 to 17.7 hours). Bioavailability of orally administered meloxicam was calculated as 72% (40% to 125%; n = 5). No adverse effects were evident following meloxicam administration via either route.
CONCLUSIONS AND CLINICAL RELEVANCE
Meloxicam administered PO at 1.0 mg/kg has good bioavailability with slow elimination kinetics in sheep. These data suggested that meloxicam may be clinically useful, provided the safety and analgesic efficacy of meloxicam as well as feed-related influences on its pharmacokinetics are established in ruminants.
Topics: Administration, Oral; Animals; Area Under Curve; Biological Availability; Female; Half-Life; Injections, Intravenous; Male; Meloxicam; Sheep; Thiazines; Thiazoles
PubMed: 23627392
DOI: 10.2460/ajvr.74.5.779