NEW YORK (Reuters Health) - The cyclooxygenase inhibiting nitric oxide donator (CINOD) AZD3582 may offer pain relief accompanied by gastrointestinal protection, researchers report in the November issue of Gut.
Dr. C. J. Hawkey of University Hospital, Nottingham, UK and colleagues observe that CINODs aim to reduce the gastrointestinal toxicity experienced with standard nonsteroidal anti-inflammatory drugs. This may be so because nitric oxide can replicate many of the gastroprotective actions of prostaglandins.
The CINOD AZD3582, a nitroxybutyl derivative of naproxen, appears safe in animals. To determine its gastrointestinal effects in humans, the team conducted a three-period crossover study in 31 volunteers.
They were randomized to 12 days of treatment with naproxen 500 mg twice daily, AZD3582 750 mg twice daily or to placebo.
There was a significant difference in the mean number of erosions in the stomach following ADZ3582 treatment (3.2) compared to that following naproxen (8.8). This was also true of the duodenum (0.9 versus 2.7)
In addition, naproxen caused a significant rise in the small intestine permeability ratio. This was not the case with AZD3382 or placebo.
The researchers also note that the steady state availability of naproxen metabolized from AZD3582 was 95% of that achieved by direct naproxen administration.
They thus conclude that “the potential combination of effective pain relief and gastrointestinal protection offered by AZD3582 warrants further evaluation.”
Source: Gut 2003;52:1537-1542. [ Google search on this article ]
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