Recent pharmacodynamic and pharmacokinetic findings on oxaprozin

Rainsford, K. D.; Omar, Hany A.; Ashraf, Anis Q.; Hewson, Alan T.; Bunning, R.A.D.; Rishiraj, R.; Shepherd, Phil; Seabrook, R. W.

doi:10.1163/156856002321168204

Cited by 25 publications

(21 citation statements)

References 82 publications

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“…(Table 1) is a non-selective COX inhibitor NSAID with effective anti-inflammatory, analgesic and antipyretic effects. These therapeutic activities derive from its capability to inhibit COX-2 [37][38][39][40][41][42]. Oxaprozin has an aliphatic propionic acid function attached to the oxazole as side chain, however contrarily to other propionic acid compounds this doesn't possess a chiral centre [40,42].…”

Section: Chemical Classificationmentioning

confidence: 99%

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Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

et al. 2015

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Section: Chemical Classificationmentioning

confidence: 99%

“…Oxaprozin highly binds to plasma proteins (99.9%) with high affinity what leads to a long plasma elimination with a half-life of 50 to 60 hours. This elevated duration of action allows the administration of a single oxaprozin dose per day of 600 to 1800 mg [32,39,40,42,43].…”

Section: Drugmentioning

confidence: 99%

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

et al. 2015

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“…Among them, oxaprozin, an achiral oxazole-propionic acid derivative (4,5-diphenyl-2-oxazolepropionic acid) (Davies, 1998), is characterized by a relatively high rate of accumulation in inflamed synovium, compared with that detectable in plasma and synovial fluids (Kurowski and Thabe, 1989;Rainsford et al, 2002). In particular, following oral administration of 1200 mg of oxaprozin for 2.5 days to patients with rheumatoid arthritis, the drug concentrations in synovial tissue averaged 25 mg·mL -1 (@85.2 mmol·L -1 ), whereas the concentrations in plasma and in synovial fluids were, respectively, 4.9-7.6 mg·mL -1 (16.7-25.9 mmol·L -1 ) and 10-17 mg·mL -1 (34-58 mmol·L -1 ) (Todd and Brogden, 1986).…”

Section: Introductionmentioning

confidence: 99%

“…When the direct action of oxaprozin on COX was examined, it was found to inhibit COX activities with an IC 50 for human platelet COX-1 of 2.2 mmol·L -1 and an IC50 for IL-1-stimulated human synovial cell COX-2 of 36 mmol·L -1 (Kawai et al, 1998). In other words, oxaprozin-mediated inhibition of COX-2 is observed at drug concentrations easily achievable in inflamed joints (Kurowski and Thabe, 1989;Rainsford et al, 2002). Thus, as the biological effects of NSAIDs are generally explained on the basis of their inhibitory action on COXs (Vane and Botting, 1998), a similar inhibitory action of oxaprozin on COX-2 inhibition would be expected to contribute substantially to its anti-inflammatory effects.…”

Section: Introductionmentioning

confidence: 99%

Delayed apoptosis of human monocytes exposed to immune complexes is reversed by oxaprozin: role of the Akt/IκB kinase/nuclear factor κB pathway

Ottonello

Bertolotto

Montecucco³

et al. 2009

British J Pharmacology

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Background and purpose: Monocytes-macrophages play a key role in the initiation and persistence of inflammatory reactions. Consequently, these cells represent an attractive therapeutic target for switching off overwhelming inflammatory responses. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drugs for the symptomatic treatment of rheumatic diseases. Their effects have been explained on the basis of cyclooxygenase (COX) inhibition. However, some of the actions of these drugs are not related to inhibition of prostaglandin synthesis. Experimental approach: We examined the effect of oxaprozin on apoptosis of immune complex-activated monocytes in comparison with drugs of the same class, and the signalling pathway that leads activated monocytes exposed to oxaprozin to apoptosis. In particular, we studied the activity of caspase-3, the involvement of IkB kinase (IKK)-nuclear factor kB (NF-kB) system and the activity of X-linked mammalian inhibitor of apoptosis protein (XIAP), Akt and mitogen-activated protein kinase (MAPK) in activated monocytes in the presence of oxaprozin. Key results: Immune complexes caused the inhibition of monocyte apoptosis. Oxaprozin reversed in a dose-dependent manner immune complex-induced survival of monocytes, without affecting the apoptosis of resting cells. Other NSAIDs are ineffective. The activity of oxaprozin was related to inhibition of Akt activation that, in turn, prevented p38 MAPK, IKK and NF-kB activation. Consistently, the inhibition of NF-kB activation reduced the production of the anti-apoptotic molecule XIAP, leading to uncontrolled activity of caspase 3. Conclusions and implications:These results suggest that oxaprozin exerts its anti-inflammatory activity also through COXindependent pathways. It is likely that oxaprozin-mediated inhibition of the Akt/IKK/NF-kB pathway contributes to its anti-inflammatory properties. Pharmacology (2009) 157, 294-306; doi:10.1111/j.1476-5381.2009 published online 26 March 2009 Keywords: apoptosis; Akt; IKK; NF-kB; NSAIDs; oxaprozin; monocytes; immune complexes Abbreviations: COX, cyclooxygenase; ERK, extracellular signal-regulated kinase; FcR, fragment crystallizable receptor; IC, immune complex; IKK, IkB kinase; IL, interleukin; JNK, Jun N-terminal kinase; MAPK, mitogen-activated protein kinase; MCP-1, monocyte chemotactic protein 1; M-CSF, macrophage-colony stimulating factor; NF-kB, nuclear factor kB; NSAIDs, non-steroidal anti-inflammatory drugs; TNF-a, tumour necrosis factor-a; XIAP, X-linked mammalian inhibitor of apoptosis protein British Journal of IntroductionThe inflammation that characterizes rheumatic diseases is usually accompanied by swelling, stiffness and considerable pain which can limit the ability to perform daily activities, reduce overall joint functions and negatively interfere with health-related quality of life (Pollard et al., 2005;Scott et al., 2005). Understanding the molecular mechanisms that underpin the processes of inflammation and pain is the topic of considerable research, with t...

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“…This compound has been shown to be effective in in vitro and animal models of inflammation, pain and pyrexia 1 and has subsequently been shown to be effective and well tolerated in the clinical management of signs and symptoms of adult rheumatoid arthritis (RA), osteoarthritis (OA), ankylosing spondylitis, soft tissue disorders such as bursitis and tendonitis, and post operative dental pain 2 .…”

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confidence: 99%

Oxaprozin: kinetic and dynamic profile in the treatment of pain

Kean

2004

Current Medical Research and Opinion

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Recent pharmacodynamic and pharmacokinetic findings on oxaprozin

Cited by 25 publications

References 82 publications

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

Oxaprozin-Loaded Lipid Nanoparticles towards Overcoming NSAIDs Side-Effects

Delayed apoptosis of human monocytes exposed to immune complexes is reversed by oxaprozin: role of the Akt/IκB kinase/nuclear factor κB pathway

Oxaprozin: kinetic and dynamic profile in the treatment of pain

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