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Veterinary and Comparative Oncology Jun 2023Reports on canine frontal sinus carcinomas (FSCs) are scarce. This retrospective review of 41 dogs with FSC (2001-2022) describes demographic and clinical...
Reports on canine frontal sinus carcinomas (FSCs) are scarce. This retrospective review of 41 dogs with FSC (2001-2022) describes demographic and clinical characteristics of canine FSC and reports the clinical experience and overall survival following treatment with toceranib phosphate (TOC) and meloxicam in 10 cases. Median age at diagnosis was 10.6 years (range: 6.5-15.4 years). There was a male-to-female-ratio of 2.4:1. The most common breeds were Jack Russell Terriers (JRT) (n = 7; 17.1%) and Rottweilers (n = 3, 7.3%). Mesocephalic breeds (70.6%) were most commonly affected, brachycephalics accounted for 8.8%. The most frequent clinical signs included skull deformation dorsomedial to the eye (87.5%), pain/head-shyness (40.0%), ocular (22.5%)/nasal (17.5%) discharge, and exophthalmos (17.5%). Duration of symptoms prior to diagnosis varied from a few days to 9 months. There were no neurological signs at initial presentation despite imaging evidence of osteolysis of the lamina interna of the frontal bone in most dogs (69.4%). In 11.5%, pulmonary changes suggestive of metastasis or concurrent primary pulmonary neoplasia were present. Tumour types included squamous cell carcinoma (58.5%), unspecified carcinoma (29.3%), and adenocarcinoma (9.8%). Ten dogs were treated with TOC (median 2.8 mg/kg EOD or three times per week) and meloxicam (0.1 mg/kg, EOD) (TOC-M), resulting in subjective regression of skull deformity in 8/10 (80.0%) patients. Overall median survival time with TOC-M was 183.5 days (range: 120-434 days). FSCs typically present with skull deformation, but no overt neurological signs. Male dogs and JRT may be overrepresented. The use of TOC-M in FSC appears promising and warrants further prospective evaluation.
Topics: Dogs; Animals; Male; Female; Meloxicam; Frontal Sinus; Dog Diseases; Paranasal Sinus Neoplasms; Carcinoma, Squamous Cell; Mouth Neoplasms; Retrospective Studies; Pyrroles
PubMed: 36745079
DOI: 10.1111/vco.12880 -
Journal of Pharmacy & Bioallied Sciences 2022Mastitis has well-recognized harmful effects on dairy farm profitability. Furthermore, mastitis impairs the milk component synthesizing ability of secretary tissues.... (Review)
Review
Mastitis has well-recognized harmful effects on dairy farm profitability. Furthermore, mastitis impairs the milk component synthesizing ability of secretary tissues. Various therapies are available for the treatment of clinical mastitis. Meloxicam exhibits preferential binding to Cyclooxygenase-2 (COX-2) receptor and consequently generates fewer negative gastrointestinal side effects than nonspecific COX inhibitors such as flunixin meglumine and ketoprofen. Toward this end, research efforts directed at understanding the use of meloxicam alone and in combination with other antibiotics to improve milk quality and production. Therefore, in this review, we have highlighted the mechanism, biopharmaceutical challenges, and merits of meloxicam usage in dairy cattle mastitis. In addition, we also presented the integration of artificial neural network, docking, and nanotechnology-driven topical drug delivery cargo as future opportunity for efficient delivery of meloxicam in the management of clinical mastitis.
PubMed: 36506727
DOI: 10.4103/jpbs.jpbs_649_21 -
Drugs Jul 2021Prolonged-release (PR; as ascribed in the EU) or extended-release (as ascribed in the USA) bupivacaine/meloxicam (HTX-011; hereafter referred to as bupivacaine/meloxicam... (Review)
Review
Prolonged-release (PR; as ascribed in the EU) or extended-release (as ascribed in the USA) bupivacaine/meloxicam (HTX-011; hereafter referred to as bupivacaine/meloxicam PR; Zynrelef) is a synergistic fixed-dose combination (FDC) of the local anaesthetic bupivacaine and the NSAID meloxicam. It is approved in the EU and the USA to treat postoperative pain. After needle-free application at the surgical site, the novel polymer technology allows simultaneous diffusion of bupivacaine and meloxicam over 72 h. In clinical trials, bupivacaine/meloxicam PR significantly reduced postoperative pain and opioid consumption relative to bupivacaine hydrochloride (HCl) and placebo in patients undergoing bunionectomy, herniorrhaphy or total knee arthroplasty (TKA). When used as the foundation of a scheduled non-opioid multimodal analgesia (MMA) regimen, bupivacaine/meloxicam PR further improved pain control and reduced the need for opioids following surgery. Bupivacaine/meloxicam PR was generally well tolerated, with a lower incidence of opioid-related adverse events than bupivacaine HCl and placebo. Although additional data would be beneficial, current evidence indicates that bupivacaine/meloxicam PR is a promising non-opioid treatment option for the management of postoperative pain.
Topics: Analgesics, Opioid; Anesthetics, Local; Anti-Inflammatory Agents, Non-Steroidal; Bupivacaine; Delayed-Action Preparations; Drug Combinations; Drug Interactions; Humans; Meloxicam; Pain, Postoperative
PubMed: 34228280
DOI: 10.1007/s40265-021-01551-9 -
Veterinary and Comparative Oncology Dec 2021This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose...
This study aims to evaluate the efficacy and side effects of low dose cyclophosphamide chemotherapy plus meloxicam as an adjuvant treatment, compared with high dose doxorubicin or surgery alone in cats with mammary carcinoma. Medical records of 228 female cats treated for mammary carcinoma between 2008 and 2018, were reviewed in eight veterinary institutions. Only cats with complete tumour staging and radical mastectomy were included in the study. One hundred and thirty-seven cats were divided into three treatment groups: group 1 (n = 80) cats treated with surgery, group 2 (n = 34) cats that had surgery and adjuvant treatment with doxorubicin, and group 3 (n = 23) cats with surgery and adjuvant treatment with low dose metronomic cyclophosphamide and meloxicam. The study endpoints were disease free interval (DFI) and overall survival (OS). Toxicity was evaluated according to the VCOG-CTCAE criteria. The median DFI was 270, 226 and 372 days in groups 1, 2 and 3, respectively. The median OS was 338 (group 1), 421 (group 2) and 430 (group 3) days. The differences between groups were not significant (DFI P = .280 and OS P = .186). Toxicity was observed in 52.9% (n = 18) of cats in group 2 and 39.1% (n = 9) of cats in group 3, with mild to moderate intensity. Differences were not significant (P = .306). In conclusion, adjuvant chemotherapy treatment did not improve survival and the overall benefit remains unproven. Randomized prospective trials are necessary to clarify the effectiveness of adjuvant chemotherapy treatment for feline mammary carcinomas.
Topics: Adjuvants, Immunologic; Animals; Antineoplastic Combined Chemotherapy Protocols; Carcinoma; Cat Diseases; Cats; Chemotherapy, Adjuvant; Cyclophosphamide; Doxorubicin; Female; Mammary Neoplasms, Animal; Mastectomy; Meloxicam; Retrospective Studies; Survival Rate
PubMed: 33140523
DOI: 10.1111/vco.12660 -
Journal of Feline Medicine and Surgery Dec 2022Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of...
OBJECTIVES
Non-steroidal anti-inflammatory drugs (NSAIDs) are infrequently utilized in cats due to concern for renal compromise; however, recent studies demonstrate tolerability of low dose meloxicam. Toceranib phosphate is used to treat several feline cancers and is well tolerated. This study aimed to determine the tolerability and adverse event profile of combined toceranib and low dose meloxicam in cancer-bearing cats. Secondary goals involved assessing anticancer tumor efficacy and impact upon quality of life and analgesia.
METHODS
Cats with any cancer not involving the kidneys were eligible. The study adopted a conventional 3 + 3 dose escalation design. Toceranib was administered every other day at a standard dose with meloxicam administered in an escalating fashion in subsequent cohorts, at a starting dose of 0.01 mg/kg on opposite days to toceranib, up to a maximum of 0.02 mg/kg daily, based upon previous safety studies. Laboratory work, blood pressure, tumor measurements, pain score and client-completed quality-of-life surveys were recorded every 2-4 weeks during the 12-week study period.
RESULTS
Twenty-one cats were enrolled. When combined with toceranib, a meloxicam dose of 0.02 mg/kg q24h was safe and well tolerated, with no cats being withdrawn due to adverse events from the drug combination. The majority of cats demonstrated clinical benefit with stable to mildly improved tumor measurements, quality of life and pain scores.
CONCLUSIONS AND RELEVANCE
Low dose meloxicam combined with toceranib is safe and well tolerated in cancer-bearing cats. Continued patient recruitment and data collection are needed to determine the maximum tolerated dose of meloxicam. The results of our study will guide further phase II/III trials.
Topics: Animals; Cats; Cat Diseases; Meloxicam; Neoplasms; Pain; Quality of Life
PubMed: 34923878
DOI: 10.1177/1098612X211067023 -
The Annals of Pharmacotherapy Jan 2023To review data for bupivacaine/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects. (Review)
Review
OBJECTIVE
To review data for bupivacaine/meloxicam extended-release (ER) solution for management of postoperative pain and opioid-sparing effects.
DATA SOURCES
Literature search of PubMed (1946 to August 2021) and ProQuest (1946 to August 2021) was performed using the terms: Zynrelef, HTX-011, and "bupivacaine AND meloxicam." Additional information sources include ClinicalTrials.gov, prescribing information, Heron Therapeutics' Clinical and Economic Evidence Dossier, meeting abstracts, and references of identified articles.
STUDY SELECTION AND DATA EXTRACTION
Clinical trials and articles evaluating bupivacaine/meloxicam ER for postoperative pain management.
DATA SYNTHESIS
Bupivacaine is a short-acting local anesthetic. Its efficacy is negatively impacted by the acidic environment of surgical sites. Meloxicam, a nonsteroidal antiinflammatory, reduces inflammation at the surgical site and increases pH propagating bupivacaine movement into the neurons. In Phase 2 and Phase 3 clinical trials, bupivacaine/meloxicam ER was compared with bupivacaine HCl, bupivacaine ER, and meloxicam ER with and without scheduled nonopioid multimodal analgesia (MMA) in bunionectomies, herniorrhaphies, total knee arthroplasty and abdominoplasty. Postoperative pain was well controlled for 72 hours and consistently superior to placebo, with minimal or no opioid use. Wound healing was not impacted and adverse effects were similar to placebo (most commonly nausea, dizziness, constipation, and headaches).
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE
Bupivacaine/meloxicam ER is a viable, safe, nonopioid local anesthetic for sustained 72-hour postoperative pain management mitigating opioid consumption.
CONCLUSION
Bupivacaine/meloxicam ER is the only dual-acting, extended-release local anesthetic available. It provides effective analgesia in the postoperative setting and successfully reduces or eliminates postoperative opioid consumption.
Topics: Humans; Anesthetics, Local; Analgesics, Opioid; Meloxicam; Bupivacaine; Pain, Postoperative
PubMed: 35536151
DOI: 10.1177/10600280221086639 -
Veterinary Anaesthesia and Analgesia Nov 2023To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg in...
OBJECTIVE
To determine the pharmacokinetics and bioavailability of meloxicam following intravenous (IV), intramuscular (IM), and oral administrations at a dose of 1.0 mg kg in Pekin ducks.
STUDY DESIGN
Randomized experimental trial.
ANIMALS
A total of 18 clinically healthy male Pekin ducks.
METHODS
Pekin ducks were randomly assigned to three groups of six ducks: IV, IM and oral. Meloxicam (1.0 mg kg) was administered to each Pekin duck. A non-compartmental analysis was used to evaluate pharmacokinetic parameters.
RESULTS
No local or systemic adverse effects were observed in any bird. Meloxicam was detected in the plasma up to 120 hours following IV, IM or oral administration. The elimination half-life of the IV route was slightly shorter than that of the IM and oral routes (p < 0.05). Following IV administration, volume of distribution at steady state and total clearance were 133.17 mL kg and 6.68 mL kg hour, respectively. The mean absorption time was 2.29 hours for IM and 1.13 hours for oral route. There were significant differences between IM and oral administration for the peak plasma concentration (C), time to reach C and bioavailability (p < 0.05).
CONCLUSIONS AND CLINICAL RELEVANCE
Meloxicam showed long elimination half-life and high bioavailability following IM and oral administration. Meloxicam in Pekin ducks provided the effective therapeutic concentration indicated in other species for up to 48 hours. However, there is a need to determine the clinical efficacy of meloxicam in Pekin ducks.
Topics: Male; Animals; Meloxicam; Ducks; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Area Under Curve; Half-Life; Injections, Intravenous; Administration, Oral; Injections, Intramuscular; Administration, Intravenous
PubMed: 37620232
DOI: 10.1016/j.vaa.2023.07.007 -
Molecules (Basel, Switzerland) Mar 2021Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes...
Recently, the design of new biological metal-ligand complexes has gained a special interest all over the world. In this research, new series of mixed ligand complexes from meloxicam (Hmel) and glycine (Gly) were synthesized. Structures of the compounds were investigated employing elemental analyses, infrared, electronic absorption, H NMR, thermal analyses, effective magnetic moment and conductivity. The estimated molar conductivity of the compounds in 1 × 10 M DMF solution indicates the non-electrolyte existence of the examined complexes. Additionally, the effective magnetic moment values refer to the complexes found as octahedral molecular geometry. The data of the infrared spectra showed the chelation of Hmel and Gly with metal ions from amide oxygen and nitrogen of the thyizol groups of Hmel and through nitrogen of the amide group and oxygen of the carboxylic group for Gly. Thermal analyses indicated that the new complexes have good thermal stability and initially lose hydration water molecules followed by coordinated water molecules, Gly and Hmel. The kinetic parameters were calculated graphically using Coats-Redfern and Horowitz-Metzeger methods at = 1 and ≠ 1. The density functional theory (DFT) calculations were performed at B3LYP levels. The optimized geometry of the ligand and its complexes were obtained based on the optimized structures. The data indicated that the complexes are soft with η value in the range 0.114 to 0.086, while η = 0.140 for free Hmel. The new prepared complexes were investigated as antibacterial and antifungal agents against some phyto- and human pathogens and the minimum inhibitory concentration (MIC) data showed that complex () has the lowest MIC for and (10.8 µg/mL).
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Coordination Complexes; Escherichia coli; Ions; Kinetics; Ligands; Magnetic Resonance Spectroscopy; Meloxicam; Metals; Microbial Sensitivity Tests; Molecular Structure; Schiff Bases; Spectrophotometry, Infrared; Thermodynamics
PubMed: 33803210
DOI: 10.3390/molecules26051480 -
BMC Veterinary Research Sep 2020The 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...
BACKGROUND
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.
RESULTS
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).
CONCLUSIONS
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
PubMed: 32938437
DOI: 10.1186/s12917-020-02556-4 -
Journal of the American Association For... Jan 2022The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg...
The nonsteroidal anti-inflammatory drugs meloxicam and carprofen are commonly used as analgesics in mice. The current recommended doses of meloxicam at 0.2-1.0 mg/kg once daily and carprofen at 5-10 mg/kg twice daily may not be adequate to provide analgesia in mice. Several studies have suggested that doses up to 20 mg/kg of meloxicam and carprofen are needed to provide analgesic efficacy. This study investigated the clinical safety of these higher doses of meloxicam and carprofen by evaluating their potential for renal and gastrointestinal toxicity. Female CD-1 mice were given 20 mg/kg of either meloxicam, carprofen, or an equivalent volume of saline subcutaneously once daily for 3 or 7 d. On day 4, mice treated for 3 d were euthanized, and on days 8 and 15, mice treated for 7 d were euthanized. Blood was collected by cardiocentesis for serum chemistry analysis. Feces was collected from the colon for fecal occult blood testing, and tissues were collected for histopathology. No clinically significant changes in serum chemistry profiles were found in the drug-treated mice at any time point as compared with the saline controls. Fecal occult blood and histologic evidence of gastritis was associated with meloxicam administration in mice evaluated at days 4 and 8. By day 15, there was no association with meloxicam treatment and the presence of fecal occult blood or gastritis. There was no association between fecal occult blood and gastritis in the carprofen or saline-treated mice regardless of the treatment durations. These findings suggest that 20 mg/kg of meloxicam in mice causes gastric toxicity when given for 3 or 7 d and should be used cautiously; however, carprofen at 20 mg/kg appears to have minimal toxic effects with regard to the parameters measured.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Carbazoles; Female; Meloxicam; Mice; Thiazines; Thiazoles
PubMed: 34920791
DOI: 10.30802/AALAS-JAALAS-21-000071