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Drugs Oct 1986Oxaprozin is a newer non-steroidal anti-inflammatory drug advocated for use in painful rheumatic and inflammatory conditions. As is the case with some other newer... (Review)
Review
Oxaprozin is a newer non-steroidal anti-inflammatory drug advocated for use in painful rheumatic and inflammatory conditions. As is the case with some other newer non-steroidal anti-inflammatory drugs, oxaprozin offers the convenience of once-daily administration. Published data suggest that oxaprozin 1200 mg once daily is comparable in effectiveness with usual dosages of aspirin, ibuprofen, indomethacin, naproxen, piroxicam and sulindac in the treatment of rheumatoid arthritis and osteoarthritis. More controlled clinical trials in adequate numbers of patients are necessary to evaluate its potential in other rheumatic and inflammatory conditions. Oxaprozin produced fewer gastrointestinal side effects than aspirin, and the short term tolerability of oxaprozin was similar to that of other non-steroidal anti-inflammatory drugs. If further definition of its efficacy and tolerability compared with other non-steroidal anti-inflammatory drugs during long term therapy confirms these initially favourable results, then oxaprozin would appear to offer a useful and convenient alternative in the treatment of painful rheumatic and inflammatory conditions.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Biological Availability; Drug Interactions; Humans; Joint Diseases; Kinetics; Oxaprozin; Propionates
PubMed: 3536423
DOI: 10.2165/00003495-198632040-00001 -
Clinical Pharmacokinetics Dec 1998Oxaprozin is a nonsteroidal anti-inflammatory drug which reaches peak plasma concentrations 2 to 6 hours after oral administration. Oxaprozin binds extensively, in a... (Review)
Review
Oxaprozin is a nonsteroidal anti-inflammatory drug which reaches peak plasma concentrations 2 to 6 hours after oral administration. Oxaprozin binds extensively, in a concentration-dependent manner, to plasma albumin. The area under the plasma concentration-time curve (AUC) of oxaprozin is linearly proportional to the dose for oral doses up to 1200 mg. At doses greater than 1200 mg there is an increase in the unbound fraction of drug, leading to an increased clearance and volume of distribution (Vd) of total oxaprozin. Accumulation of the drug at steady state is between 40 and 58% lower than predicted by single dose data. After administration of multiple doses, the apparent oral clearance (CL/F) and Vd of total oxaprozin increased while those of the unbound drug decreased significantly. Substantial concentrations of oxaprozin are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Relationships between total plasma, unbound plasma and synovial concentrations, and therapeutic and toxicological effects have yet to be established. Oxaprozin is eliminated following biotransformation to glucuroconjugated metabolites which are excreted in urine and bile, with little drug being eliminated unchanged. Two hydroxylated metabolites have been shown to possess anti-inflammatory activity. Hepatic disease and rheumatoid arthritis do not significantly alter the disposition of oxaprozin. Patients with renal impairment demonstrate an increase in unbound plasma concentrations of oxaprozin. A significant drug interaction has been demonstrated between oxaprozin and aspirin (acetylsalicylic acid).
Topics: Age Factors; Anti-Inflammatory Agents, Non-Steroidal; Dose-Response Relationship, Drug; Drug Interactions; Heart Failure; Humans; Kidney Diseases; Liver Diseases; Oxaprozin; Propionates
PubMed: 9884815
DOI: 10.2165/00003088-199835060-00002 -
Clinical Pharmacy Jul 1992The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of oxaprozin are reviewed. Oxaprozin, a nonsteroidal anti-inflammatory drug (NSAID)... (Review)
Review
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of oxaprozin are reviewed. Oxaprozin, a nonsteroidal anti-inflammatory drug (NSAID) under consideration for approval by the Food and Drug Administration, is characterized as a propionic acid. By inhibiting cyclo-oxygenase, oxaprozin decreases the formation of prostaglandin (PG) precursors from arachidonic acid, resulting in decreased PG biosynthesis and reduced pain and inflammatory responses. Oxaprozin is well absorbed after oral administration, and peak plasma concentration is reached in three to six hours. Oxaprozin is primarily eliminated by urinary excretion of the unchanged drug. It has a long elimination half-life and persists in synovial fluid. In clinical studies, oxaprozin was equally or more effective than aspirin and as effective as naproxen in the treatment of rheumatoid arthritis. For treatment of osteoarthritis, oxaprozin was as effective as naproxen and more effective than aspirin or piroxicam. Studies have also shown oxaprozin to be effective therapy for juvenile rheumatoid arthritis and ankylosing spondylitis. Oxaprozin, like other NSAIDs, can cause gastrointestinal adverse effects. Other possible adverse effects include allergic reactions, analgesic nephropathy, hepatotoxicity, and increased bleeding times. For adults, the anticipated daily dosage is 600-1200 mg given as a single dose for rheumatoid arthritis, osteoarthritis, and analgesia. In children, oxaprozin 10-20 mg/kg/day has been used to treat juvenile rheumatoid arthritis. Oxaprozin is as effective as other NSAIDs and offers once-daily dosing; however, it does not offer any therapeutic advantage over other currently available NSAIDs.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Drug Interactions; Humans; Oxaprozin; Propionates
PubMed: 1617910
DOI: No ID Found -
Chemical Biology & Drug Design May 2019Oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) is a non-steroidal, analgesic and antipyretic propionic acid derivative, whose activity in treating inflammatory...
Oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) is a non-steroidal, analgesic and antipyretic propionic acid derivative, whose activity in treating inflammatory disorders is well known. The aim of this study was to investigate the ability of oxaprozin to modulate the activity of matrix metalloproteinase 9 (MMP-9), a zinc-dependent endopeptidase involved in a wide range of physiological and pathological events associated with extracellular matrix (ECM) remodelling. The interaction between oxaprozin and MMP-9 was firstly investigated in silico by molecular docking and analysis with LIGPLOT software. Subsequently, the potential inhibitory activity of oxaprozin against MMP-9 and the possible mechanism of the ligand-enzyme interaction were investigated in vitro. Taking into account the in silico findings, MMP-9 can be considered a potential target of oxaprozin, which seems to be able to chelate the catalytic zinc ion through the nitrogen of the oxazole ring and the carboxylate moiety. Moreover, one of the phenyl rings interact with the S1' inhibitor-binding pocket through hydrophobic interaction. Gelatin zymography and enzymatic inhibition assay confirmed the potential role of oxaprozin as a competitive inhibitor of MMP-9. These observations sound particularly interesting if we consider the pathological role of MMP-9, especially evident in inflammatory conditions and cancer. This work may represent a starting point to improve the understanding of the role of oxaprozin, as well as its structural analogues, in modulating the MMP-9 function.
Topics: Binding Sites; Humans; Kinetics; Ligands; Matrix Metalloproteinase 9; Molecular Docking Simulation; Oxaprozin; Protein Structure, Tertiary; Recombinant Proteins; Software
PubMed: 30582279
DOI: 10.1111/cbdd.13468 -
Current Medical Research and Opinion Aug 2004Oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) is a non-steroidal anti-inflammatory drug (NSAID) which is effective in models of inflammation, pain and pyrexia. It is...
Oxaprozin (4,5-diphenyl-2-oxazolepropionic acid) is a non-steroidal anti-inflammatory drug (NSAID) which is effective in models of inflammation, pain and pyrexia. It is effective and well tolerated in the clinical management of adult rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis, soft tissue disorders and post operative dental pain. Oxaprozin has a high oral bioavailability (95%), with peak plasma concentrations at 3 to 5 hours after dosing. It is metabolised in the liver by oxidative and conjugative pathways and readily eliminated by the renal and faecal routes. Oxaprozin's strong analgesic qualities are particularly useful in painful musculoskeletal conditions such as periarthritis of the shoulder, since it exhibits actions such as inhibition of COX-1 and COX-2 isoenzymes, inhibition of nuclear translocation of NF-kappaB and of metalloproteases, and modulates the endogenous cannabinoid system. This editorial addresses the accompanying paper by Barbara Heller and Rosanna Tarricone on the management of shoulder periarthritis pain, in which they studied the efficacy and safety of oxaprozin compared to the comparator drug diclofenac over a 15 day period. Both oxaprozin and diclofenac compared well in the primary study endpoint of reduction in shoulder pain. Oxaprozin and diclofenac were well tolerated and oxaprozin showed better improvement in shoulder function and in the mental health item of the SF-36 quality of life component. The study by Heller and Tarricone is an addition to the large number of clinical trials which demonstrate that oxaprozin has equal efficacy in comparison with standard doses of commonly used anti-rheumatic agents such as aspirin, diclofenac, ibuprofen, indomethacin etc. in several different painful musculoskeletal conditions.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antirheumatic Agents; Diclofenac; Humans; Oxaprozin; Periarthritis; Propionates; Shoulder Joint; Shoulder Pain; Treatment Outcome
PubMed: 15324530
DOI: 10.1185/030079904125004420 -
Archives of Dermatology Dec 1996
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diagnosis, Differential; Drug Eruptions; Humans; Male; Middle Aged; Oxaprozin; Photosensitivity Disorders; Porphyrias; Porphyrins; Propionates; Skin Diseases, Vesiculobullous
PubMed: 8961891
DOI: No ID Found -
Archiv Der Pharmazie Feb 2018Oxaprozin is a popular non-steroidal anti-inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In...
Oxaprozin is a popular non-steroidal anti-inflammatory drug (NSAID) and its chronic oral use is clinically restricted due to its gastrointestinal (GI) complications. In order to circumvent the GI complications, oxaprozin was amended as a prodrug in a one-pot reaction using N,N-carbonyldiimidazole as an activating agent. Dextran of average molecular weight (60,000-90,000 Da) was exploited as a carrier in the process of oxaprozin prodrug production by esterification. The structural profiles of the synthesized oxaprozin prodrug were characterized by FT-IR and NMR spectroscopy. The oxaprozin prodrug possessed optimal molecular weight, lipophilicity, partition coefficient, protein binding, and degree of substitution of 52.4%. The release of oxaprozin upon hydrolysis of the prodrug in both simulated gastric fluid and simulated intestinal fluid followed first-order kinetics with 55.2 min of half-life. Varied ADME properties of the prodrug resulted upon Schrodinger's QikProp tool application. Oxaprozin prodrug displayed significant analgesic, antipyretic, and anti-inflammatory activities, with a remarkable decrease in the ulcer index and being devoid of antigenicity in experimental animals. Thus, it is evident that oxaprozin prodrug is a safer oral NSAID without causing any ulcerations.
Topics: Analgesics; Animals; Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Carrageenan; Dose-Response Relationship, Drug; Edema; Female; Hydrolysis; Male; Molecular Structure; Molecular Weight; Oxaprozin; Prodrugs; Propionates; Rats; Rats, Wistar; Structure-Activity Relationship; Ulcer
PubMed: 29283449
DOI: 10.1002/ardp.201700256 -
Pharmaceutical Research Feb 2016Nanostructured Lipid Carriers (NLCs) loading oxaprozin were developed to address an effective drug packaging and targeted delivery, improving the drug pharmacokinetics...
PURPOSE
Nanostructured Lipid Carriers (NLCs) loading oxaprozin were developed to address an effective drug packaging and targeted delivery, improving the drug pharmacokinetics and pharmacodynamics properties and avoiding the local gastric side-effects. Macrophages actively phagocyte particles with sizes larger than 200 nm and, when activated, over-express folate beta receptors - features that in the case of this work constitute the basis for passive and active targeting strategies.
METHODS
Two formulations containing oxaprozin were developed: NLCs with and without folate functionalization. In order to target the macrophages folate receptors, a DSPE-PEG2000-FA conjugate was synthesized and added to the NLCs.
RESULTS
These formulations presented a relatively low polydispersity index (approximately 0.2) with mean diameters greater than 200 nm and zeta potential inferior to -40 mV. The encapsulation efficiency of the particles was superior to 95% and the loading capacity was of 9%, approximately. The formulations retained the oxaprozin release in simulated gastric fluid (only around 10%) promoting its release on simulated intestinal fluid. MTT and LDH assays revealed that the formulations only presented cytotoxicity in Caco-2 cells for oxaprozin concentrations superior to 100 μM. Permeability studies in Caco-2 cells shown that oxaprozin encapsulation did not interfered with oxaprozin permeability (around 0.8 × 10(-5) cm/s in simulated intestinal fluid and about 1.45 × 10(-5) cm/s in PBS). Moreover, in RAW 264.7 cells NLCs functionalization promoted an increased uptake over time mainly mediated by a caveolae uptake mechanism.
CONCLUSIONS
The developed nanoparticles enclose a great potential for oxaprozin oral administration with significant less gastric side-effects.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Caco-2 Cells; Cell Line; Drug Carriers; Folic Acid; Humans; Mice; Nanoparticles; Oxaprozin; Permeability; Phosphatidylethanolamines; Polyethylene Glycols; Propionates
PubMed: 26350105
DOI: 10.1007/s11095-015-1788-x