Nombre impressionnant d'articles Auj. à 03:10
scientifiques sortis ce mois-ci dans les grandes revues medicales sur le naproxcinod, notamment dans le American Journal of Medicine (pas moins !).
Ce flux d'articles est ideal pour finaliser un dossier FDA.
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Am J Med. 2009 May;122(5 Suppl)
16-22. Links
Treatment of patients with hypertension and arthritis pain: new concepts.Weber MA.
Downstate College of Medicine, State University of New York, Brooklyn, New York 10022, USA.
[email protected]
Arthritis pain often occurs concurrently with hypertension and other cardiovascular risk factors. Treating patients with hypertension who have arthritis and other painful conditions can be a challenge because of potential risks associated with the agents commonly used to treat pain and inflammation. Hypertension is associated with endothelial dysfunction and decreased bioavailability of nitric oxide (NO). Naproxcinod, an investigational drug, is the first in a new class of agents called cyclooxygenase-inhibiting NO donators. They differ from traditional nonsteroidal anti-inflammatory drugs in their ability to donate NO, a signaling molecule known to have potentially beneficial effects on the vasculature and the gastrointestinal tract. Naproxcinod, by donating NO, offers a therapeutic option that might mitigate the negative blood pressure effects and adverse gastrointestinal effects associated with traditional arthritis therapies. This article reviews some preliminary preclinical and clinical studies of key safety data of an investigational new NO-donating anti-inflammatory agent.
Expert Opin Biol Ther. 2009 May;9(5):649-57. Links
Naproxcinod, a new cyclooxygenase-inhibiting nitric oxide donator (CINOD).Geusens P.
University Hasselt, University Hospital, The Netherlands.
[email protected]
BACKGROUND: COX-inhibiting nitric oxide donators (CINODs) are a new class of drugs that combine the actions of the parent COX inhibitor with nitric oxide (NO), with the aim of reducing potential toxicity of the parent drug, while maintaining its analgesic and anti-inflammatory effects. AZD3582 (Naproxcinod) is the first in the class of CINODs. OBJECTIVE/METHODS: To review the effects of NO donation, CINODS in general and naproxen in osteoarthritis (OA), based on literature in PubMed. RESULTS: In preclinical and human studies, this drug produced similar analgesic and anti-inflammatory effects to its parent naproxen, with improved gastrointestinal safety in OA patients. The results of recent clinical trials, which were designed to study effects on blood pressure, are expected shortly, after peer-review. CONCLUSIONS: As naproxen is considered the safest COX inhibitor choice from a cardiovascular perspective, AZD3582 has the potential to become a new drug treatment in patients with OA, in whom pain and function are not controlled by the use of analgesics.
J Rheumatol. 2009 May 1. [Epub ahead of print] Links
Efficacy, Safety, and Tolerability of the Cyclooxygenase-Inhibiting Nitric Oxide Donator Naproxcinod in Treating Osteoarthritis of the Hip or Knee.Karlsson J, Pivodic A, Aguirre D, Schnitzer TJ.
From Sahlgrenska University Hospital/Ostra, Goteborg, Sweden; NicOx S.A, Sophia Antipolis, France; and Northwestern University, Chicago, Illinois, USA.
OBJECTIVE: Naproxcinod, a cyclooxygenase-inhibiting nitric oxide donator antiinflammatory drug, was evaluated in this phase 2, double-blind, randomized, parallel group study to determine its optimal dose in patients with osteoarthritis (OA). METHODS: In total 543 patients with OA of the hip or knee were randomized to receive naproxcinod 750 mg once daily (qd), 750 mg twice daily (bid), 1125 mg bid, rofecoxib 25 mg qd, or placebo for 6 weeks. The primary efficacy variable was the within-patient change from baseline to the average of Weeks 4 and 6 in WOMAC pain subscale score. Treatment-group differences were compared using ANCOVA with factors for treatment and country, and baseline pain subscale score as a covariate. Safety endpoints included vital signs and adverse events. Treatment-group differences in mean change from baseline toWeek 6 in systolic blood pressure (SBP) were compared using an ANCOVA with treatment and country as fixed factors and baseline SBP as covariate. RESULTS: All active treatments showed statistically significant reductions in WOMAC pain score compared to placebo (p </= 0.02). Naproxcinod was well tolerated. The 750 mg bid dose appeared to have the best balance of benefit versus safety. All 3 naproxcinod doses showed a reduction in SBP, while an increase was shown for rofecoxib. The changes for the naproxcinod groups were statistically significantly better compared to rofecoxib (p </= 0.02). CONCLUSION: This dose-finding study identified naproxcinod 750 mg bid as the upper dose for further therapeutic confirmatory clinical trials. Naproxcinod at all doses decreased mean SBP compared to an increase with rofecoxib.
PMID: 19411388 [PubMed - as supplied by publisher]
chi è stato attento lo sa! 
