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Australian Veterinary Journal Jan 2019To evaluate the efficacy of the non-steroidal anti-inflammatory drug, meloxicam, in alleviating pain and inflammation and on production-related variables in a model of...
OBJECTIVE
To evaluate the efficacy of the non-steroidal anti-inflammatory drug, meloxicam, in alleviating pain and inflammation and on production-related variables in a model of sterile acute inflammation in sheep.
METHODS
Groups of 12 mature Merino ewes received 0, 0.5, 1.0 or 1.5 mg/kg meloxicam subcutaneously 90 min before injection of 0.1 mL turpentine subcutaneously on the anterior aspect of the proximal phalanx of a forelimb. Pain- and inflammation-related variables were assessed at -18, 3, 6, 9, 12, 24, 48 and 72 h relative to meloxicam administration. Daily feed intake and body weight change 7 days later were also assessed. Pain-related variables measured were weight borne on each forelimb, lameness score, time each forelimb was raised in a 20-s interval and tolerance to a noxious mechanical stimulus. Inflammation-related variables measured were skin temperature, limb circumference, body temperature, plasma haptoglobin concentration and peripheral blood leucocyte parameters.
RESULTS
Meloxicam was effective in improving all pain-related variables. A dose-dependent response was seen between 0 and 1.0 mg/kg, with no additional benefit provided by 1.5 mg/kg. At a dose rate of 1.0 mg/kg, meloxicam improved weight borne on the turpentine-treated limb by 14%, reduced the time the treated limb was held in a non-weight-bearing posture by 46%, reduced the lameness score by 58% and improved tolerance to pressure by 52%. No significant effects of meloxicam on inflammatory variables or appetite were observed.
CONCLUSIONS
Using a validated pain model, the data suggested that 1.0 mg/kg meloxicam provided significant analgesic benefits to sheep.
Topics: Administration, Intravenous; Analysis of Variance; Animals; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Female; Irritants; Lameness, Animal; Meloxicam; New South Wales; Pain; Pain Measurement; Random Allocation; Sheep; Sheep Diseases; Skin Temperature; Turpentine; Weight-Bearing
PubMed: 30693494
DOI: 10.1111/avj.12779 -
Toxicology Jul 2020Thiazoles are biologically active aromatic heterocyclic rings occurring frequently in natural products and drugs. These molecules undergo typically harmless elimination;...
Thiazoles are biologically active aromatic heterocyclic rings occurring frequently in natural products and drugs. These molecules undergo typically harmless elimination; however, a hepatotoxic response can occur due to multistep bioactivation of the thiazole to generate a reactive thioamide. A basis for those differences in outcomes remains unknown. A textbook example is the high hepatotoxicity observed for sudoxicam in contrast to the relative safe use and marketability of meloxicam, which differs in structure from sudoxicam by the addition of a single methyl group. Both drugs undergo bioactivation, but meloxicam exhibits an additional detoxification pathway due to hydroxylation of the methyl group. We hypothesized that thiazole bioactivation efficiency is similar between sudoxicam and meloxicam due to the methyl group being a weak electron donator, and thus, the relevance of bioactivation depends on the competing detoxification pathway. For a rapid analysis, we modeled epoxidation of sudoxicam derivatives to investigate the impact of substituents on thiazole bioactivation. As expected, electron donating groups increased the likelihood for epoxidation with a minimal effect for the methyl group, but model predictions did not extrapolate well among all types of substituents. Through analytical methods, we measured steady-state kinetics for metabolic bioactivation of sudoxicam and meloxicam by human liver microsomes. Sudoxicam bioactivation was 6-fold more efficient than that for meloxicam, yet meloxicam showed a 6-fold higher efficiency of detoxification than bioactivation. Overall, sudoxicam bioactivation was 15-fold more likely than meloxicam considering all metabolic clearance pathways. Kinetic differences likely arise from different enzymes catalyzing respective metabolic pathways based on phenotyping studies. Rather than simply providing an alternative detoxification pathway, the meloxicam methyl group suppressed the bioactivation reaction. These findings indicate the impact of thiazole substituents on bioactivation is more complex than previously thought and likely contributes to the unpredictability of their toxic potential.
Topics: Activation, Metabolic; Biotransformation; Chemical and Drug Induced Liver Injury; Electrons; Epoxy Compounds; Humans; Hydroxylation; In Vitro Techniques; Kinetics; Meloxicam; Metabolic Networks and Pathways; Microsomes, Liver; Thiazines; Thiazoles
PubMed: 32437779
DOI: 10.1016/j.tox.2020.152478 -
International Immunopharmacology Mar 2023Meloxicam is a selective cyclooxygenase-2 inhibitor and has been widely used in combination with antibiotics to alleviate uterine inflammation and provide analgesia in...
Meloxicam is a selective cyclooxygenase-2 inhibitor and has been widely used in combination with antibiotics to alleviate uterine inflammation and provide analgesia in postpartum cows. Studies have shown that meloxicam has antioxidant and anti-inflammatory effects. However, the link between meloxicam and uterine inflammation and oxidative stress in dairy cows has not been studied. The purpose of this study was to research the effects of meloxicam (0.5 or 5 μM) on oxidative stress and inflammatory response of primary bovine endometrial epithelial cells (BEEC) stimulated by Escherichia coli lipopolysaccharide (1 μg/mL LPS). As a result, LPS stimulated the production of oxidative stress markers and the expression of inflammatory factors, accompanied by a decrease in the activity and the gene transcription of antioxidant enzymes. Co-treatment of meloxicam and LPS reduced the content of oxidative stress markers and the mRNA levels of the pro-inflammatory genes, and improved antioxidant enzyme activities and the corresponding gene expression as compared with the cells treated with LPS alone. Meloxicam attenuated the inhibitory effect of the Nrf2 pathway and the phosphorylation levels of p65 and IκBα caused by LPS. In conclusion, meloxicam alone had no effect on BEEC, but prevented oxidative stress and inflammatory response in LPS-stimulated BEEC.
Topics: Female; Cattle; Animals; NF-kappa B; Meloxicam; Lipopolysaccharides; NF-E2-Related Factor 2; Antioxidants; Oxidative Stress; Inflammation; Epithelial Cells
PubMed: 36750013
DOI: 10.1016/j.intimp.2023.109822 -
Journal of Feline Medicine and Surgery Feb 2021Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival....
OBJECTIVES
Meloxicam therapy may benefit cats with degenerative joint disease, and retrospective studies suggest it could slow kidney disease progression and increase survival. This study aimed to prospectively evaluate the renal effects of low-dose meloxicam treatment (0.02 mg/kg/day) over 6 months in cats with chronic kidney disease (CKD).
METHODS
Twenty-one cats with stable International Renal Interest Society stage 2 or 3 CKD were recruited and randomized to placebo or meloxicam groups. Cats were evaluated at baseline and at 1, 3 and 6 months, including blood pressure, chemistry, symmetric dimethylarginine (SDMA), glomerular filtration rate (GFR), urinalysis, urine protein:creatinine ratio (UPC), urine transforming growth factor-beta (β):creatinine ratio, urine clusterin, urine cystatin B and serum inosine.
RESULTS
No statistical difference was observed in systolic blood pressure, blood urea nitrogen, creatinine, SDMA, GFR, urine transforming growth factor-β:creatinine ratio, urine clusterin, urine cystatin B or serum inosine in cats receiving meloxicam vs placebo. Mean UPC was greater in the meloxicam group (0.33) than the placebo group (0.1) at 6 months ( = 0.006). Four cats had meloxicam discontinued owing to potential (mainly gastrointestinal) adverse effects.
CONCLUSIONS AND RELEVANCE
No decline in renal excretory function was observed when meloxicam was administered to cats with CKD. However, gastrointestinal adverse effects were observed, and cats that received meloxicam had greater proteinuria at 6 months than cats that received placebo. As proteinuria is associated with negative outcomes (progression of azotemia and hypertension) in cats with CKD, this finding suggests that meloxicam should be used with caution in cats with CKD and UPC monitored. Until further research is available, clinicians should weigh the risk of potential increased proteinuria against quality of life benefits when considering meloxicam for analgesia in cats with renal disease.
Topics: Animals; Cat Diseases; Cats; Glomerular Filtration Rate; Meloxicam; Quality of Life; Renal Insufficiency, Chronic; Retrospective Studies
PubMed: 32594827
DOI: 10.1177/1098612X20935750 -
European Journal of Pharmaceutical... Aug 2022Intranasally administered non-steroidal anti-inflammatory drugs (NSAIDs) offer an innovative opportunity in the field of pain management. Combination of the nasal...
Intranasally administered non-steroidal anti-inflammatory drugs (NSAIDs) offer an innovative opportunity in the field of pain management. Combination of the nasal physiological advantages such as the rich vascularization and large absorption area along with novel nanomedical formulations can fulfill all the necessary criteria of an advanced drug delivery system. Nanoemulsions represent a versatile formulation approach suitable for nasal drug delivery by increasing the absorption and the bioavailability of many drugs for systemic and nose-to-brain delivery due to their stability, small droplet size and optimal solubilization properties. In this study we aimed to develop meloxicam (MX)-loaded mucoadhesive nanoemulsions and to investigate the nasal applicability of the optimized formulations. Our results indicated the optimized nanoemulsion formulation (MX-NE3) had a droplet size of 158.5 nm in monodisperse droplet size distribution (polydispersity index of 0.211). The surface charge was -11.2 mV, which helped with the colloidal stability upon dilution at simulated nasal conditions and storage. The high encapsulation efficiency (79.2%) mediated a 15-fold drug release and a 3-fold permeability increase at nasal conditions compared to the initial MX. Proper wetting properties associated with high mucoadhesion prosper the increased residence time on the surface of the nasal mucosa. No cytotoxic effect of the formulations was observed on NIH/3T3 mouse embryonic fibroblast cell lines, which supports the safe nasal applicability.
Topics: Administration, Intranasal; Animals; Drug Delivery Systems; Emulsions; Fibroblasts; Meloxicam; Mice; Nasal Mucosa; Particle Size
PubMed: 35662634
DOI: 10.1016/j.ejps.2022.106229 -
Journal of Dairy Science Feb 2022A promising strategy to improve newborn calf survival could be the administration of nonsteroidal antiinflammatory drugs (NSAID) especially in cases of low vitality...
A promising strategy to improve newborn calf survival could be the administration of nonsteroidal antiinflammatory drugs (NSAID) especially in cases of low vitality calves born from difficult calvings. The objective of this clinical trial was to determine the effect of a single-dose meloxicam treatment [target dosage = 0.5 mg/kg ad usum veterinarium (A.U.V.) injection] on parameters of lying behavior of Holstein-Friesian dairy calves (n = 180) born to eutocic (n = 98) compared with dystocic dams (n = 82). Animal-based measures included newborn calf vitality (low, 1-6 scores; normal, 7-12 scores, scored immediately after birth), calf sex and birth weight, parity of the dam, and early maternal behavior (the time spent licking the calf). Parameters of the complex lying behavior were recorded during the first 48 h after delivery and included (1) the time spent standing, (2) lying down frequency, (3) the longest standing bout, (4) the average duration of standing bouts, (5) the first successful standing, and (6) the first attempt to stand. None of the parameters related to lying behavior were influenced by the parity of the dam, calf sex, or birth weight and maternal grooming behavior. The latency and the first attempt to stand were not influenced by the NSAID treatment; however, the time spent standing, the longest standing bout, and the average duration of standing indicated increased standing ability of meloxicam-treated calves with low vitality, but not in normal-vitality calves. The latency to stand and first attempt to stand were both increased by dystocia. Based on the present findings, sensory measurement of parameters of lying behavior during the immediate neonatal period might be useful to evaluate the efficiency of NSAID protocols. A single-dose meloxicam treatment showed considerable promise for improving standing ability of low-vitality calves.
Topics: Animals; Behavior, Animal; Cattle; Dystocia; Female; Meloxicam; Parity; Parturition; Pregnancy
PubMed: 34799121
DOI: 10.3168/jds.2021-20704 -
Pain Management May 2021Meloxicam for intravenous use (meloxicam iv.) is a nanocrystal formulation with improved dissolution properties and shortened time to peak plasma concentrations versus...
Meloxicam for intravenous use (meloxicam iv.) is a nanocrystal formulation with improved dissolution properties and shortened time to peak plasma concentrations versus oral meloxicam. In Phase III and IIIb trials, 30 mg once daily relieved pain following pre- or postoperative administration in orthopedic, abdominal and colorectal surgeries. Meloxicam iv. was associated with reduced opioid consumption, the clinical benefit of which remains unclear. The drug may be administered alone or in combination with other non-nonsteroidal anti-inflammatory drugs. In Phase III trials, it demonstrated adverse event profile similar to placebo, with nausea, constipation, vomiting and headache occurring most frequently. Meloxicam iv. does not appear to adversely affect platelet function or wound-healing parameters. No new safety signals were detected in the Phase IIIb studies.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Meloxicam; Pain Measurement; Pain, Postoperative; Treatment Outcome
PubMed: 33291975
DOI: 10.2217/pmt-2020-0082 -
Contraception Jun 2001The nonsteroidal antiinflammatory, selective cyclo-oxygenase-2 (COX-2) inhibitor, meloxicam, was tested to assess its effect on rabbit ovulation. Meloxicam in different...
The nonsteroidal antiinflammatory, selective cyclo-oxygenase-2 (COX-2) inhibitor, meloxicam, was tested to assess its effect on rabbit ovulation. Meloxicam in different doses was administered intraperitoneally (ip) to adult female Californian rabbits at 2, 5, 8, and 24 h postcoitus with sperm-positive rabbits. Rabbits were killed on Day 10 of gestation. Meloxicam produced significant inhibition of ovulation in rabbits. This inhibition of ovulation by meloxicam was dose- and time-dependent. Ovulation in rabbits was completely inhibited by a single ip administration of meloxicam (20 mg/kg) when the drug was administered at 2 and 5 h postcoitus, whereas neither ovulation nor implantation were inhibited (pregnancy rate 75%) by the same dose administered 24 h postcoitus (approximately 14 h post ovulation). Further, ovulation was completely inhibited by 10 mg/kg of meloxicam when the drug was administered at 5 or 8 h postcoitus, but there was less inhibition of ovulation when 10 mg/kg of the drug was administered at 2 or 24 h postcoitus (pregnancy rate 25 and 80%, respectively). Corpora lutea, maternal plasma progesterone, ovary fresh weight, and maternal body weight gain were affected by meloxicam treatment. Histopathological findings observed in the ovaries of treated rabbits included microscopic dilatation of graffian follicles, particularly mature follicles. Some of the follicles were cystically dilated in addition to severe hemorrhage within the follicles which lost ova. These results show that ovulation can be inhibited in rabbits by meloxicam. Further studies are needed to assess the value of selective COX-2 inhibitors as potential nonhormonal contraceptive agents.
Topics: Animals; Cyclooxygenase Inhibitors; Female; Indomethacin; Meloxicam; Ovary; Ovulation; Pregnancy; Rabbits; Thiazines; Thiazoles
PubMed: 11672556
DOI: 10.1016/s0010-7824(01)00207-4 -
Journal of Veterinary Pharmacology and... Sep 2022The objective of this study was to determine the pharmacokinetics of meloxicam after a single intravenous (IV), intramuscular (IM), and oral (PO) dose at 1 mg/kg body...
The objective of this study was to determine the pharmacokinetics of meloxicam after a single intravenous (IV), intramuscular (IM), and oral (PO) dose at 1 mg/kg body weight in Jing Hong laying hens. Blood samples were collected at predetermined time points. Plasma meloxicam concentrations were determined using a validated high-performance liquid chromatography (HPLC) assay method and then subjected to a non-compartmental analysis. After IV administration, meloxicam had a mean (±SD) volume of distribution at steady-state (Vd ) of 206.50 ± 25.23 ml/kg, a terminal half-life (t ) of 5.45 ± 0.53 h, and a total body clearance (Cl) of 26.48 ± 4.13 ml/h/kg. After PO and IM administration, meloxicam was absorbed relatively rapidly: the peak concentrations (C s) of 3.04 ± 0.56 and 8.94 ± 2.31 μg/ml were observed at 3.08 and 0.80 h, respectively. After PO and IM administration, the absolute bioavailability (F) was determined as 70.13% and 125.50%, respectively. Assuming that hens shared the same analgesic threshold of meloxicam (0.5 μg/ml) with humans, the plasma concentrations after three different routes (PO, IM, and IV) of administration were above this value for 16.7, 19.2, and 14.9 h, respectively.
Topics: Administration, Intravenous; Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Area Under Curve; Biological Availability; Chickens; Female; Half-Life; Humans; Injections, Intramuscular; Injections, Intravenous; Meloxicam
PubMed: 35717631
DOI: 10.1111/jvp.13081 -
Reumatizam 2007
Review
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Cyclooxygenase Inhibitors; Humans; Meloxicam; Rheumatic Diseases; Thiazines; Thiazoles
PubMed: 18351150
DOI: No ID Found