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Clinical Therapeutics 1995This multicenter, 6-week, double-blind, placebo-controlled, parallel-group study compared the efficacy and safety of oxaprozin 1200 mg once daily with that of nabumetone... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
This multicenter, 6-week, double-blind, placebo-controlled, parallel-group study compared the efficacy and safety of oxaprozin 1200 mg once daily with that of nabumetone 1000 mg once daily in patients with moderate-to-severe osteoarthritis (OA) of the knee. To be eligible, patients had to experience a flare of OA within 2 weeks of discontinuing their usual OA medication (nonsteroidal anti-inflammatory drug or analgesic). Eligible patients were assessed at baseline and then randomized to receive oxaprozin (n = 109), nabumetone (n = 110), or placebo (n = 109). Efficacy assessments were performed at weeks 1, 2, 4, and 6. Primary efficacy variables included knee pain on weight bearing, knee pain on motion, and patient's and physician's global assessments of OA. Secondary efficacy variables included pain intensity, time to walk 50 feet, and duration of morning stiffness. Safety was evaluated by use of routine laboratory analyses; physical examination at screening, baseline, and week 6 (or study termination); assessment of symptoms at baseline and at each visit; and testing stools for occult blood at screening and between week 4 and the final visit. Adverse events were monitored throughout the study. Between-group differences in efficacy variables were evident by week 1. The mean change in improvement from baseline with oxaprozin compared with placebo was statistically significant in favor of oxaprozin at weeks 1, 2, 4, and 6 for all primary efficacy variables. The mean change in improvement from baseline with nabumetone compared with placebo, however, was statistically significant only at week 1 for knee pain on motion, patient's global assessment, and physician's global assessment. The mean change in improvement from baseline was statistically significant (P < or = 0.035) in favor of oxaprozin versus nabumetone at weeks 2 and 6 for all four primary efficacy variables and also at week 4 for knee pain on motion. The incidence of adverse clinical events between treatment groups was not statistically significant. However, nine oxaprozin-treated patients had asymptomatic liver enzyme elevations reported as adverse events. Four of these patients had reversible elevations of aspartate aminotransferase and alanine aminotransferase greater than three times the upper limit of normal range (P < 0.05); two of these patients were taking other medications known to induce liver enzyme abnormalities. The study showed that oxaprozin 1200 mg once daily was statistically significantly more efficacious than nabumetone 1000 mg once daily for the treatment of patients with moderate-to-severe OA of the knee. Both drugs were clinically well tolerated.
Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Double-Blind Method; Female; Humans; Knee; Male; Middle Aged; Nabumetone; Osteoarthritis; Oxaprozin; Pain; Propionates
PubMed: 8565037
DOI: 10.1016/0149-2918(95)80050-6 -
Scientific Reports Jul 2022Accurate specification of the drugs' solubility is known as an important activity to appropriately manage the supercritical impregnation process. Over the last decades,...
Accurate specification of the drugs' solubility is known as an important activity to appropriately manage the supercritical impregnation process. Over the last decades, the application of supercritical fluids (SCFs), mainly CO, has found great interest as a promising solution to dominate the limitations of traditional methods including high toxicity, difficulty of control, high expense and low stability. Oxaprozin is an efficient off-patent nonsteroidal anti-inflammatory drug (NSAID), which is being extensively used for the pain management of patients suffering from chronic musculoskeletal disorders such as rheumatoid arthritis. In this paper, the prominent purpose of the authors is to predict and consequently optimize the solubility of Oxaprozin inside the COSCF. To do this, the authors employed two basic models and improved them with the Adaboost ensemble method. The base models include Gaussian process regression (GPR) and decision tree (DT). We optimized and evaluated the hyper-parameters of them using standard metrics. Boosted DT has an MAE error rate, an R2-score, and an MAPE of 6.806E-05, 0.980, and 4.511E-01, respectively. Also, boosted GPR has an R2-score of 0.998 and its MAPE error is 3.929E-02, and with MAE it has an error rate of 5.024E-06. So, boosted GPR was chosen as the best model, and the best values were: (T = 3.38E + 02, P = 4.0E + 02, Solubility = 0.001241).
Topics: Anti-Inflammatory Agents, Non-Steroidal; Humans; Machine Learning; Oxaprozin; Propionates; Solubility
PubMed: 35908085
DOI: 10.1038/s41598-022-17440-4 -
Journal of Biomedicine & Biotechnology 2009The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid...
The modulation of CD40L activity might represent a promising therapeutic target to reduce monocyte inflammatory functions in chronic diseases, such as rheumatoid arthritis. In the present study, we investigated the possible influence of nonsteroidal anti-inflammatory drugs (NSAIDs) on CD40L-induced monocyte survival. Monocytes were isolated from buffy coats by using Ficoll-Percoll gradients. Monocyte apoptosis was evaluated by fluorescence microscopy on cytopreps stained with acridine orange or using flow cytometry analysis of Annexin-V and Propidium Iodide staining. Akt and NF-kappaB activation was assessed using western blot. Caspase 3 activity was determined spectrophotometrically. Among different NSAIDs, only oxaprozin dose-dependently increased apoptosis of CD40L-treated monocytes. Oxaprozin pro-apoptotic activity was associated with the inhibition of CD40L-triggered Akt and NF-kappaB phosphorylation and the activation of caspase 3. In conclusion, our data suggest that oxaprozin-induced apoptosis in CD40L-treated human monocytes is associated with previously unknown cyclooxygenase (COX)-independent pathways. These intracellular proteins might be promising pharmacological targets to increase apoptosis in CD40L-treated monocytes.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Apoptosis; CD40 Ligand; Caspase 3; Cyclooxygenase Inhibitors; Humans; Inflammation; Mitogen-Activated Protein Kinases; Monocytes; NF-kappa B p50 Subunit; Oxaprozin; Phosphatidylinositol 3-Kinases; Phosphorylation; Propionates; Prostaglandin-Endoperoxide Synthases; Proto-Oncogene Proteins c-akt; Signal Transduction
PubMed: 19672323
DOI: 10.1155/2009/478785 -
Molecules (Basel, Switzerland) Sep 2022Over the last years, extensive motivation has emerged towards the application of supercritical carbon dioxide (SCCO) for particle engineering. SCCO has great potential...
Over the last years, extensive motivation has emerged towards the application of supercritical carbon dioxide (SCCO) for particle engineering. SCCO has great potential for application as a green and eco-friendly technique to reach small crystalline particles with narrow particle size distribution. In this paper, an artificial intelligence (AI) method has been used as an efficient and versatile tool to predict and consequently optimize the solubility of oxaprozin in SCCO systems. Three learning methods, including multi-layer perceptron (MLP), Kriging or Gaussian process regression (GPR), and k-nearest neighbors (KNN) are selected to make models on the tiny dataset. The dataset includes 32 data points with two input parameters (temperature and pressure) and one output (solubility). The optimized models were tested with standard metrics. MLP, GPR, and KNN have error rates of 2.079 × 10, 2.173 × 10, and 1.372 × 10, respectively, using MSE metrics. Additionally, in terms of R-squared, they have scores of 0.868, 0.997, and 0.999, respectively. The optimal inputs are the same as the maximum possible values and are paired with a solubility of 1.26 × 10 as an output.
Topics: Artificial Intelligence; Carbon Dioxide; Machine Learning; Oxaprozin; Solubility
PubMed: 36144490
DOI: 10.3390/molecules27185762 -
Clinical Pharmacology and Therapeutics Sep 1988The effects of renal disease on the steady-state kinetics of oxaprozin were assessed in eight patients on hemodialysis with normal serum albumin levels and eight normal... (Comparative Study)
Comparative Study
The effects of renal disease on the steady-state kinetics of oxaprozin were assessed in eight patients on hemodialysis with normal serum albumin levels and eight normal subjects who received six doses. A larger clearance and volume of distribution at steady state for total and unbound oxaprozin occurred in the patients on hemodialysis. The elimination half-lives were not different. The mean total AUC, peak concentration, average steady-state plasma concentration, and trough concentration for total and unbound oxaprozin were decreased in the patients on hemodialysis. These differences are consistent with impaired absorption of oxaprozin in patients on hemodialysis. The higher dose-averaged unbound fraction of oxaprozin in plasma in patients on hemodialysis may be caused by endogenous binding inhibitors. Because clearance was not reduced in patients on hemodialysis, the dose of oxaprozin may not need to be reduced when albumin levels are normal.
Topics: Administration, Oral; Adult; Anti-Inflammatory Agents, Non-Steroidal; Female; Humans; Kidney Failure, Chronic; Male; Middle Aged; Models, Biological; Oxaprozin; Propionates; Protein Binding; Renal Dialysis; Serum Albumin
PubMed: 3416552
DOI: 10.1038/clpt.1988.154 -
Journal of Analytical Toxicology 1999A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented....
A method for the extraction of oxaprozin from equine urine and serum and its quantitation by high-performance liquid chromatography-ultraviolet detection is presented. Confirmation of oxaprozin in postadministration extracts was accomplished by gas chromatographic- mass spectrometric analysis of methylated extracts or liquid chromatography with tandem mass spectrometry daughter ion mass spectra of underivatized extracts. Daypro, a formulation of oxaprozin, was administered orally at a dose of 4.8 g to four standardbred mares. Urine and serum samples were collected to 120 h postadministration. Base hydrolysis of equine urine before extraction resulted in an increase in the amount of oxaprozin measured, an indication of conjugation by ester formation. The urinary elimination profiles of each horse were significantly different from each other with more than one peak in oxaprozin concentration before the 29-31-h collection time. After this collection time, the differences between the oxaprozin urinary concentrations of each horse follow each other more closely. The peak average urinary concentrations of oxaprozin were 25.1 and 17.0 microg/mL at collection times of 8-10 and 18-22 h, respectively. The latest detection of oxaprozin in urine was at the last collection time of 119-121 h postadministration at a concentration close to the detection limit of approximately 0.1 microg/mL. The serum elimination profiles do not vary between horses as much as the urinary elimination profiles. The peak average serum concentration was 49.0 microg/mL at a collection time of 6 h postadministration. The latest detection was at the last collection time of 120 h. Oxaprozin is metabolized in the horse by hydroxylation. Two major urinary metabolites were isolated and identified as hydroxylated oxaprozin. The two urinary metabolites were isolated from equine postadministration urine and analyzed by mass spectrometry and proton nuclear magnetic resonance spectroscopy, which showed that the hydroxylation had occurred at the para positions of the two aromatic rings.
Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Female; Horses; Hydroxylation; Oxaprozin; Propionates; Ultraviolet Rays
PubMed: 10445486
DOI: 10.1093/jat/23.4.242 -
Nihon Yakurigaku Zasshi. Folia... May 1984Anti-inflammatory activity and mode of action of oxaprozin, a new non-steroidal anti-inflammatory agent, were investigated in experimental animal models and in vitro...
Anti-inflammatory activity and mode of action of oxaprozin, a new non-steroidal anti-inflammatory agent, were investigated in experimental animal models and in vitro tests. Anti-inflammatory potency of oxaprozin was almost equal to that of aspirin in acetic acid vascular permeability, carrageenin hind paw edema, cotton pellet granuloma and adjuvant arthritis tests in rats. On the other hand, in mice, oxaprozin was more potent than aspirin, ibuprofen and phenylbutazone, and it was as potent as sulindac and fenbufen in acetic acid vascular permeability and carrageenin hind paw edema tests. In adrenalectomized rats, the anti-edema activity of oxaprozin in the carrageenin hind paw edema test was the same as that in intact rats. Oxaprozin inhibited erythema formation induced by ultra-violet rays in guinea pigs. The inhibitory potency of oxaprozin against prostaglandin E2 biosynthesis in vitro was equal to that of ibuprofen. Oxaprozin showed a concentration-dependent inhibition of heat-induced denaturation of bovine serum albumin and lysis of rabbit erythrocytes in vitro. However, oxaprozin did not inhibit rat hind paw edemas induced by dextran, formalin and serotonin. It was suggested from these results that the mode of action of oxaprozin is similar to those of other acidic non-steroidal anti-inflammatory drugs. Ulcerogenicity of oxaprozin was weaker than those of phenylbutazone and aspirin in rats. Species differences in the metabolic rate of oxaprozin were shown. The blood concentration of oxaprozin in rats is extremely low because the metabolic rate of oxaprozin is rapid in rats. Therefore, in rats, oxaprozin exhibited a weak anti-inflammatory effect. However, in mice, oxaprozin had a low metabolic rate, and the effect of oxaprozin was as potent as sulindac and fenbufen. The elimination half-life of oxaprozin is extended, 49 to 69 hr, in humans. It was suggested from these findings that oxaprozin is a potent and long acting anti-inflammatory drug in clinical use.
Topics: Animals; Anti-Inflammatory Agents; Capillary Permeability; Cyclooxygenase Inhibitors; Disease Models, Animal; Female; Gastric Mucosa; Guinea Pigs; Hemolysis; Inflammation; Male; Mice; Oxaprozin; Propionates; Protein Denaturation; Rats; Rats, Inbred Strains
PubMed: 6432656
DOI: No ID Found -
Journal of Clinical Pharmacology Apr 1983Oxaprozin, a new nonsteroidal antiinflammatory agent, was studied alone and in combination with aspirin for its effects on hemostasis and protein binding in 10 healthy...
Oxaprozin, a new nonsteroidal antiinflammatory agent, was studied alone and in combination with aspirin for its effects on hemostasis and protein binding in 10 healthy adults. When both oxaprozin and aspirin were given separately for seven days and in combination for five days, both drugs prolonged bleeding time and inhibited collagen- and epinephrine-induced platelet aggregation to a similar degree. The effects of the combination of oxaprozin and aspirin were not additive. The data from the protein binding study showed that oxaprozin was more than 99 per cent bound to plasma proteins. Aspirin displaced oxaprozin from its binding sites. As a result, the rate of plasma clearance of oxaprozin significantly increased from 20 to 26 ml/min/kg (P less than 0.05), and the plasma half-life decreased from 45 to 40 hours. Platelet count and the humoral clotting mechanism were not affected by either drug alone or in combination. There was no clinical evidence of bleeding. One subject who received oxaprozin for 12 days and, in addition, aspirin for the last five days developed a rash that subsided after both drugs were discontinued; one subject treated with aspirin experienced tinnitus. These data suggest that oxaprozin, like aspirin and other nonsteroidal antiinflammatory drugs, should be used with caution when administered to patients who have suffered trauma, who undergo surgery, or who have known defects in hemostasis.
Topics: Adult; Anti-Inflammatory Agents; Aspirin; Bleeding Time; Blood Proteins; Collagen; Epinephrine; Female; Hemostasis; Humans; Male; Oxaprozin; Platelet Aggregation; Propionates; Protein Binding
PubMed: 6863578
DOI: 10.1002/j.1552-4604.1983.tb02717.x -
Journal of Oral and Maxillofacial... May 2010In this study, oxaprozin, a long-acting nonsteroidal anti-inflammatory drug, and naproxen sodium were compared in terms of their effects on edema, pain, and trismus... (Comparative Study)
Comparative Study Randomized Controlled Trial
Analgesic and anti-inflammatory effects of oxaprozin and naproxen sodium after removal of impacted lower third molars: a randomized, double-blind, placebo-controlled crossover study.
PURPOSE
In this study, oxaprozin, a long-acting nonsteroidal anti-inflammatory drug, and naproxen sodium were compared in terms of their effects on edema, pain, and trismus after surgery for impacted mandibular third molars.
MATERIALS AND METHODS
Thirty healthy patients with bilaterally impacted mandibular third molars were included in this randomized, cross-over, double-blind, placebo-controlled study. Patients were assigned randomly to 1 of 3 surgery groups and received postoperatively 1,200 mg oxaprozin, 550 mg naproxen sodium, or a placebo. Postoperative edema was measured with ultrasonography performed before and after surgery. Trismus was measured by comparison of preoperative and postoperative maximum interincisal mouth opening measurements by caliper. Pain was assessed by a visual analog scale (VAS) and by recording the number of rescue analgesic pills taken.
RESULTS
After removal of impacted third molars, the patients administered oxaprozin and naproxen showed superior results over those given placebo in terms of pain parameters (P < .05), but these treatments had no statistically significant effect on facial swelling. Comparing the oxaprozin and naproxen groups, there were no differences in the mouth opening measurements, but naproxen showed a statistically superior effect over the placebo (P < .05). Although not statistically significant, oxaprozin showed a more pronounced effect in reducing trismus than did the placebo (P = .07).
CONCLUSIONS
Administration of either oxaprozin or naproxen sodium during the postoperative period is effective and has similar effects in reducing pain but questionable benefit for the management of trismus. However, neither agent has clinical benefit in terms of reducing edema.
Topics: Adolescent; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Double-Blind Method; Edema; Face; Female; Humans; Male; Mandible; Molar, Third; Naproxen; Oxaprozin; Pain, Postoperative; Placebos; Propionates; Prospective Studies; Range of Motion, Articular; Tooth, Impacted; Trismus; Young Adult
PubMed: 20206429
DOI: 10.1016/j.joms.2009.09.094 -
Clinical Therapeutics 1996This 6-week, multicenter, double-masked, placebo-controlled study compared the efficacy, tolerability, and safety of the recommended starting dose of oxaprozin (1200... (Clinical Trial)
Clinical Trial Comparative Study Randomized Controlled Trial
This 6-week, multicenter, double-masked, placebo-controlled study compared the efficacy, tolerability, and safety of the recommended starting dose of oxaprozin (1200 mg/d) and a 1500-mg/d dose of nabumetone in the treatment of patients with moderate-to-severe osteoarthritis (OA) of the knee. A total of 347 patients with a mean age of 61.1 years were randomized to receive oxaprozin (116 patients), nabumetone (115 patients), or placebo (116 patients). Adults of either sex who were older than 18 years of age were eligible for entry into the study, if they had had OA of the knee for at least 6 months. Efficacy variables included knee pain on weight bearing, knee pain on motion, patients' and physicians' global assessments of OA, pain intensity as measured on a visual analog scale, and time to walk 50 feet as quickly as possible. Efficacy variables were assessed at baseline and at weeks 1, 2, 4, and 6. Between-group differences in efficacy variables were evident by week 1. Mean improvements were significantly greater with oxaprozin than with placebo for all efficacy variables at all time periods, except knee pain on motion at weeks 2 and 4 and time to walk 50 feet at weeks 1, 2, and 4. Mean improvements were significantly greater with nabumetone than with placebo for all efficacy variables at all time periods, except the following: knee pain on weight bearing at weeks 2, 4 and 6; knee pain on motion at weeks 2 and 4; patients' global assessment at week 4; and pain intensity as measured on a visual analog scale at weeks 2 and 4. There were, however, no significant differences between oxaprozin and nabumetone in any of these efficacy variables. Adverse events were reported by 83 (71.6%) patients who took oxaprozin, by 80 (69.6%) patients who took nabumetone, and by 57 (49.1%) patients who took placebo. Adverse events were reported for significantly more patients taking oxaprozin or nabumetone than placebo. However, adverse events tended to be mild or moderate and rarely resulted in patients withdrawing from the study. Combined with the results of an earlier study, the results of this study showed that a 1500-mg/d dose of nabumetone, which is higher than the recommended starting dose of 1000 mg/d, is required for efficacy equivalent to that of the recommended starting dose of oxaprozin, 1200 mg/d, in relieving the symptoms of OA. Thus nabumetone may require dosage titration from the recommended starting dose. Oxaprozin and nabumetone were found to have similar tolerability profiles, as shown by adverse-event monitoring and withdrawal rates, as well as clinically similar safety profiles, as demonstrated by physical examinations, hematologic and biochemical laboratory testing, hemoccult testing, and adverse-event monitoring and symptom assessment.
Topics: Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Butanones; Double-Blind Method; Female; Humans; Knee Joint; Male; Middle Aged; Nabumetone; Osteoarthritis; Oxaprozin; Propionates
PubMed: 8851458
DOI: 10.1016/s0149-2918(96)80184-6