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The Cochrane Database of Systematic... 2000Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly... (Review)
Review
BACKGROUND
Piroxicam is a non-steroidal anti-inflammatory drug (NSAID) with analgesic properties, and is used mainly for treating rheumatic disorders. Some drugs have been directly compared against each other within a trial setting to determine their relative efficacies, whereas other have not. It is possible, however, to compare analgesics indirectly by examining the effectiveness of each drug against placebo when used in similar clinical situations.
OBJECTIVES
To determine the analgesic efficacy and adverse effects of single-dose piroxicam compared with placebo in moderate to severe postoperative pain. To compare the effects of piroxicam with other analgesics.
SEARCH STRATEGY
Published reports were identified from systematic searching of Medline, Biological Abstracts, Embase, The Cochrane Library and the Oxford Pain Relief Database. Additional studies were identified from the reference lists of retrieved reports.
SELECTION CRITERIA
The following inclusion criteria were used: full journal publication, randomised placebo controlled trial, double-blind design, adult patients, postoperative pain of moderate to severe intensity at the baseline assessment, postoperative administration of oral or intramuscular piroxicam.
DATA COLLECTION AND ANALYSIS
Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients obtaining at least 50% pain relief. This was used to calculate estimates of relative benefit and number-needed-to-treat for one patient to obtain at least 50% pain relief. Information was collected on adverse effects and estimates of relative risk and number-needed-to-harm were calculated.
MAIN RESULTS
Three trials (141 patients) compared oral piroxicam 20 mg with placebo and one (15 patients) compared oral piroxicam 40 mg with placebo. For single doses of piroxicam 20 mg and 40 mg the respective numbers-needed-to-treat for at least 50% pain relief were 2.7 (2.1 to 3.8) [95% confidence interval] and 1.9 (1.2 to 4.3) [95% confidence interval] compared with placebo over 4-6 hours in moderate to severe postoperative pain. The reported incidence of adverse effects was no higher with piroxicam (20 mg or 40 mg) than with placebo.
REVIEWER'S CONCLUSIONS
Piroxicam appears to be of similar efficacy to other non-steroidal anti-inflammatory drugs (NSAIDs) and intramuscular morphine 10 mg when used as a single oral dose in the treatment of moderate to severe postoperative pain.
Topics: Acute Disease; Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Humans; Outcome Assessment, Health Care; Pain, Postoperative; Piroxicam; Randomized Controlled Trials as Topic
PubMed: 11034755
DOI: 10.1002/14651858.CD002762 -
Advanced Pharmaceutical Bulletin Sep 2017Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of...
Cocrystallisation of drug with coformers is a promising approach to alter the solid sate properties of drug substances like solubility and dissolution. The objective of the present work was to prepare, formulate and evaluate the piroxicam cocrystal by screening various coformers. Cocrystals of piroxicam were prepared by dry grinding method. The melting point and solubility of crystalline phase was determined. The potential cocrystal was characterized by DSC, IR, XRPD. Other pharmaceutical properties like solubility and dissolution rate were also evaluated. Orodispersible tablets of piroxicam cocrystal were formulated, optimized and evaluated using 3 factorial design. Cocrystals of piroxicam-sodium acetate revealed the variation in melting points and solubility. The cocrystals were obtained in 1:1 ratio with sodium acetate. The analysis of Infrared explicitly indicated the shifting of characteristic bands of piroxicam. The X-Ray Powder Diffraction pattern denoted the crystallinity of cocrystals and noteworthy difference in 2θ value of intense peaks. Differential scanning calorimetry spectra of cocrystals indicated altered endotherms corresponding to melting point. The pH solubility profile of piroxicam showed sigmoidal curve, which authenticated the pKa-dependent solubility. Piroxicam cocrystals also exhibited a similar pH-solubility profile. The cocrystals exhibited faster dissolution rate owing to cocrystallization as evident from 30% increase in the extent of dissolution. The orodispersible tablets of piroxicam cocrystals were successfully prepared by direct compression method using crosscarmelose sodium as superdisintegrant with improved disintegration time (30 sec) and dissolution rate. The piroxicam cocrystal with modified properties was prepared with sodium acetate and formulated as orodispersible tablets having faster disintegration and greater dissolution rate.
PubMed: 29071222
DOI: 10.15171/apb.2017.048 -
Journal of Experimental Neuroscience 2016Piroxicam is a benzothiazine compound with anti-inflammatory, antipyretic, and analgesic properties. Because of the very high efficacy of piroxicam and its increasing...
Piroxicam is a benzothiazine compound with anti-inflammatory, antipyretic, and analgesic properties. Because of the very high efficacy of piroxicam and its increasing use in the treatment of carcinomas in dogs and cats, there is a need for acute toxicity study of piroxicam in monogastric animals and its potential for causing secondary poisoning in puppies. Piroxicam manufactured by Shanxi Federal Pharmaceutical Co, Ltd. was used for this study. Revised up-and-down procedure was used for the estimation of median lethal dose in mouse (259.4 ± 51.9 mg/kg), rat (259.4 ± 69.6 mg/kg), rabbit (707.5 ± 130.8 mg/kg), cat (437.5 ± 128.1 mg/kg), guinea pig (218.7 ± 64.1 mg/kg), monkey (733.3 ± 83.3 mg/kg), broiler (285.3 ± 62.5 mg/kg), hen (638.3 ± 115.4 mg/kg), turkey (707.5 ± 130.8 mg/kg), pigeon (375 ± 55.9 mg/kg), and duck (311.3 ± 46.6 mg/kg). The acute toxicity signs of piroxicam at doses 207.5 mg/kg and above observed in the animals are torticollis, opisthotonos, somnolence, lethargy, diarrhea, gastroenteritis, generalized internal bleeding, anemia, congestion of the lung and liver, flaccid paralysis, cheesy lung, urinary incontinence, engorged urinary bladder, convulsive jerking of the limbs, lying in ventral recumbency, gasping for air, roaring, and death. Three out of six puppies died after being fed the carcasses of poisoned turkey, duck, and hen administered piroxicam at doses of 1000, 415, and 1000 mg/kg, respectively. White flaky cheesy materials observed in turkeys were also observed in the gastrointestinal content of the puppies. Paleness of carcasses, watery crop content, dryness of pericardium, gastroenteritis, intestinal perforation, and whitish pericardium were observed in broilers. There were effusions in thoracic and abdominal cavities as seen in all other carcasses poisoned primarily by piroxicam. Administration of atropine (0.02 mg/kg) led to survival of the remaining puppies. In conclusion, piroxicam is very to moderately toxic in monogastric animals.
PubMed: 27773993
DOI: 10.4137/JEN.S40144 -
Molecules (Basel, Switzerland) Jun 2020Drug concentration plays an important role in the interaction with drug carriers affecting the kinetics of release process and toxicology effects. Cyclodextrins (CDs)...
Drug concentration plays an important role in the interaction with drug carriers affecting the kinetics of release process and toxicology effects. Cyclodextrins (CDs) can solubilize hydrophobic drugs in water enhancing their bioavailability. In this theoretical study based on molecular mechanics and molecular dynamics methods, the interactions between β-cyclodextrin and piroxicam, an important nonsteroidal anti-inflammatory drug, were investigated. At first, both host-guest complexes with native β-CD in the 1:1 and in 2:1 stoichiometry were considered without assuming any initial a priori inclusion: the resulting inclusion complexes were in good agreement with literature NMR data. The interaction between piroxicam and a β-CD nanosponge (NS) was then modeled at different concentrations. Two inclusion mechanisms were found. Moreover, piroxicam can interact with the external NS surface or with its crosslinkers, also forming one nanopore. At larger concentration, a nucleation process of drug aggregation induced by the first layer of adsorbed piroxicam molecules is observed. The flexibility of crosslinked β-CDs, which may be swollen or quite compact, changing the surface area accessible to drug molecules, and the dimension of the aggregate nucleated on the NS surface are important factors possibly affecting the kinetics of release, which shall be theoretically studied in more detail at specific concentrations.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Drug Carriers; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Molecular Dynamics Simulation; Piroxicam; beta-Cyclodextrins
PubMed: 32575617
DOI: 10.3390/molecules25122848 -
TheScientificWorldJournal 2012Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment...
Cyclooxygenase (COX) inhibitors, already widely used for the treatment of pain and inflammation, are considered as promising compounds for the prevention and treatment of neoplasia. The aim of our study was to determine the direct antiproliferative effects of nonsteroidal anti-inflammatory drugs (NSAIDs), piroxicam and deracoxib, at a variety of concentrations as both single and combined treatments on canine mammary carcinoma cell line CMT-U27 and to understand the mechanisms of cell death. MTT assay was performed to determine cell viability, and flow cytometric analyses were performed to evaluate apoptosis and cell cycle alterations. Significant decrease in cell viability was observed at high concentrations of piroxicam and deracoxib in both single and combined treatments after 72 h incubation. Combined treatment produced a significantly greater inhibition than that caused by either agent alone. Also apoptotic cell number was increased by both drugs at the cytotoxic concentrations. However, concomitant treatment of cells with piroxicam and deracoxib resulted in significant induction of apoptosis at lower concentrations and accumulation of cells in the G₀/G₁ phase. Significant cytotoxic effects exhibited by the combination of piroxicam and deracoxib against canine mammary carcinoma cells in vitro suggest an attractive approach for the treatment of canine mammary carcinoma.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Survival; Cyclooxygenase Inhibitors; Dogs; Dose-Response Relationship, Drug; Female; Mammary Neoplasms, Animal; Piroxicam; Sulfonamides
PubMed: 23251109
DOI: 10.1100/2012/976740 -
The Journal of Veterinary Medical... Apr 2021The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole...
A combined protocol with piroxicam, chemotherapy, and whole pelvic irradiation with simultaneous boost volumetric modulated arc radiotherapy for muscle-invasive canine urinary transitional cell carcinoma: First clinical experience.
The aims of this pilot study were to evaluate the feasibility and efficacy of high-dose hypofractionated volumetric modulated arc radiotherapy (VMAT) applied to whole pelvic region radiotherapy (WPRT) with multilevel simultaneous integrated boost (MLSIB) combined with piroxicam and chemotherapy for the treatment of canine transitional cell carcinoma (TCC) of the lower urinary tract with muscle invasion TCC. Twelve dogs were enrolled, according to stage, in two groups: group 1, TCC confined to the urinary tract; group 2, TCC with metastasis. The planning target volume dose was tailored from 36 to 42 Gy in 6 fractions. All dogs were prescribed piroxicam and radiosensitizing carboplatin, and six received chemotherapy after radiotherapy. Serial follow-ups with computed tomography and magnetic resonance imaging were performed. Disease control and toxicity effects were evaluated according to the Response Evaluation Criteria in Solid Tumors and Veterinary Radiation Therapy Oncology Group criteria. The treatment was well tolerated, and no high-grade side effects were reported. The median overall survival times for groups 1 and 2 were 1,230 and 150 days, respectively. A considerable percentage of patients in group1 (50%) were still alive at the time of writing this paper, and a longer follow-up could enable a more accurate survival analysis. This preliminary analysis shows that VMAT applied to the WPRT with MLSIB is an effective and safe option for dogs with lower urinary TCC, although the presence of metastases worsens the prognosis.
Topics: Animals; Carcinoma, Transitional Cell; Dog Diseases; Dogs; Muscles; Pelvis; Pilot Projects; Piroxicam; Radiotherapy, Intensity-Modulated; Urinary Bladder
PubMed: 32963177
DOI: 10.1292/jvms.19-0662 -
Cellular and Molecular Gastroenterology... 2021p21-activated kinase-1 (PAK1) belongs to a family of serine-threonine kinases and contributes to cellular pathways such as nuclear factor-κB (NF-κB), mitogen-activated...
BACKGROUND & AIMS
p21-activated kinase-1 (PAK1) belongs to a family of serine-threonine kinases and contributes to cellular pathways such as nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT), and Wingless-related integration site(Wnt)/β-catenin, all of which are involved in intestinal homeostasis. Overexpression of PAK1 is linked to inflammatory bowel disease as well as colitis-associated cancer (CAC), and similarly was observed in interleukin (IL)10 knockout (KO) mice, a model of colitis and CAC. Here, we tested the effects of PAK1 deletion on intestinal inflammation and carcinogenesis in IL10 KO mice.
METHODS
IL10/PAK1 double-knockout (DKO) mice were generated and development of colitis and CAC was analyzed. Large intestines were measured and prepared for histology or RNA isolation. Swiss rolls were stained with H&E and periodic acid-Schiff. Co-immunoprecipitation and immunofluorescence were performed using intestinal organoids, SW480, and normal human colon epithelial cells 1CT.
RESULTS
When compared with IL10 KO mice, DKOs showed longer colons and prolonged crypts, despite having higher inflammation and numbers of dysplasia. Crypt hyperproliferation was associated with Notch1 activation and diminished crypt differentiation, indicated by a reduction of goblet cells. Gene expression analysis indicated up-regulation of the Notch1 target hairy and enhancer of split-1 and the stem cell receptor leucin-rich repeat-containing G-protein-coupled receptor 5 in DKO mice. Interestingly, the stem cell marker olfactomedin-4 was present in colonic tissue. Increased β-catenin messenger RNA and cytoplasmic accumulation indicated aberrant Wnt signaling. Co-localization and direct interaction of Notch1 and PAK1 was found in colon epithelial cells. Notch1 activation abrogated this effect whereas silencing of PAK1 led to Notch1 activation.
CONCLUSIONS
PAK1 contributes to the regulation of crypt homeostasis under inflammatory conditions by controlling Notch1. This identifies a novel PAK1-Notch1 axis in intestinal pathophysiology of inflammatory bowel disease and CAC.
Topics: Animals; Cell Line; Colitis; Colitis-Associated Neoplasms; Colon; Disease Models, Animal; Female; Gene Silencing; Humans; Interleukin-10; Intestinal Mucosa; Male; Mice; Mice, Knockout; Organoids; Piroxicam; Primary Cell Culture; Receptor, Notch1; Up-Regulation; Wnt Signaling Pathway; p21-Activated Kinases
PubMed: 33189893
DOI: 10.1016/j.jcmgh.2020.11.001 -
Biomedicine & Pharmacotherapy =... Oct 2020Piroxicam (PM) is an oxicam-NSAID commonly recommended for various pain and associated inflammatory disorders. However, it is reported to have a gastric and hepato-renal...
Piroxicam (PM) is an oxicam-NSAID commonly recommended for various pain and associated inflammatory disorders. However, it is reported to have a gastric and hepato-renal toxic effect. Therefore, the current research was planned to investigate the possible mechanisms behind the mitigating action of the coenzyme (CoQ10), a natural, free radical scavenger, against PM tissue injury. Rats were assigned to five equal groups; Control, CoQ10 (10 mg/kg, orally), PM (7 mg/kg, i.p.), CoQ + PM L, and CoQ + PM H group. After 28 days, PM provoked severe gastric ulceration and marked liver and kidney damage indicated by an elevated gastric ulcer index and considerable alteration in liver and kidney biochemical tests. The toxic effects might be attributed to mitochondrial dysfunction and excess generation of reactive oxygen species (ROS), as indicated by enhanced malondialdehyde (MDA) levels along with decreased reduced-glutathione (GSH) levels and catalase (CAT) activity. Apoptotic cell death also was demonstrated by increased regulation of activated caspase-3 in the stomach, liver, and kidney tissues. Interestingly, external supplementation of CoQ10 attenuated the PM-inflicted deleterious oxidative harm and apoptosis. This ameliorative action was ascribed to the free radical scavenging activity of CoQ10.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; COVID-19; Caspase 3; Dietary Supplements; Free Radical Scavengers; Kidney; Liver; Male; Malondialdehyde; Oxidation-Reduction; Oxidative Stress; Piroxicam; Rats; Rats, Wistar; Reactive Oxygen Species; Stomach; Stomach Ulcer; Ubiquinone
PubMed: 34321156
DOI: 10.1016/j.biopha.2020.110627 -
Biomedicine & Pharmacotherapy =... Feb 2019Piroxicam (Px) is a non-steroidal anti-inflammatory drug that is widely prescribed in various inflammatory disorders. However, Px is known to induce gastric ulceration...
Piroxicam (Px) is a non-steroidal anti-inflammatory drug that is widely prescribed in various inflammatory disorders. However, Px is known to induce gastric ulceration and hepato-renal toxicity. Rosuvastatin (ROSV), a member of the statin family, has anti-inflammatory and antioxidant actions independent of its anti-hyperlipidemic action. Therefore, we investigated the protective effects of ROSV against Px-induced gastric, liver, and kidney injury. Five groups of seven rats each were used; control group, ROSV group (20 mg/kg, given orally), Px group (7 mg/kg, given intraperitoneally), Px+ROSV L (7 and 10 mg/kg, respectively), and Px+ROSV H (7 and 20 mg/kg, respectively) group. The results revealed that Px induced severe gastric mucosal damage expressed by high ulcer index along with significant increases in liver and kidney function parameters including AST, ALT, creatinine, and urea. Disrupted lipid metabolism also was observed in Px-treated animals. Moreover, marked an increase in malondialdehyde (MDA) and decreases in glutathione (GSH) and catalase (CAT) levels along with enhanced activated caspase-3 expression in the gastric, hepatic, and renal tissues following Px-insult suggested a possible involvement of lipid peroxidation in Px-induced gastropathy and hepatorenal toxicity. However, in a dose-dependent manner, ROSV was able to mitigate Px-induced lipid peroxidation and apoptosis in gastric, liver, and kidney tissues.
Topics: Animals; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kidney; Lipid Peroxidation; Liver; Male; Piroxicam; Random Allocation; Rats; Rats, Wistar; Reactive Oxygen Species; Rosuvastatin Calcium; Stomach Ulcer
PubMed: 30572194
DOI: 10.1016/j.biopha.2018.11.004 -
Bioinformation 2022Zaltoprofen, a unique propionic acid group of NSAIDs, works by blocking the enhancing effects of bradykinin along with the COX-2 enzyme. Therefore, it is of interest to...
Zaltoprofen, a unique propionic acid group of NSAIDs, works by blocking the enhancing effects of bradykinin along with the COX-2 enzyme. Therefore, it is of interest to evaluate the acute and chronic anti-inflammatory (arthritic) potential of zaltoprofen versus piroxicam in Murine models. A total of 48 Wister rats (200-250 g) of either sex (24 in each model) were used in the present study. The anti-inflammatory and arthritic potential of zaltoprofen was evaluated and compared by Carrageenan-induced acute inflammation and formalin-induced chronic inflammation. There was a significant inhibition of paw volume (P<0.001) on different time scales with two different doses of the test compound (Zaltoprofen 10 & 20 mg/kg) in the acute inflammation model compared to the negative control (NaCl 10 ml/kg). However, in the chronic inflammation model, zaltoprofen 10 mg/kg and 20 mg/kg doses of the test compound showed a significant reduction in chronic inflammation, comparable to the negative control (NaCl 10 ml/kg), although the potency was lower than the positive control (piroxicam 10 mg/kg) (P 0.05). Thus, zaltoprofen shows significant anti-inflammatory and arthritic effects in both acute and chronic models by inhibiting various inflammatory mediators.
PubMed: 37426507
DOI: 10.6026/97320630018752