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Scand J Gastroenterol. 2006 Mar;41(3):264-73.

Dose-effect comparisons of the CINOD AZD3582 and naproxen on upper gastrointestinal tract mucosal injury in healthy subjects.

Author information

1
Gastroenterology Group Practice, Brain-Gut Research Group, Berne, Switzerland.

Abstract

OBJECTIVE:

The objective of this endoscopic study was to compare the effects on the gastroduodenal mucosa of healthy volunteers of different doses and dosing regimens of AZD3582, a cyclooxygenase-inhibiting nitric oxide donator (CINOD), with equimolar doses of naproxen.

MATERIAL AND METHODS:

Healthy volunteers were enrolled in a single-centre, randomized, double-blind, crossover trial consisting of two 12-day treatment periods and employing six sequences. The groups were: AZD3582 750 mg daily versus 375 mg twice daily (n=25), AZD3582 375 mg twice daily versus 750 mg twice daily (n=25) and naproxen 250 mg twice daily versus 500 mg twice daily (n=25).

RESULTS:

Gastroduodenal tract damage was similar with AZD3582 375 mg twice daily and 750 mg twice daily (mean number of erosions and ulcers+/-SD: 2.88+/-3.95 versus 3.08+/-2.80, respectively; p=0.824; 1 ulcer counted as 10 erosions). There was an indication of decreased gastroduodenal toxicity with AZD3582 750 mg daily compared with 375 mg twice daily (0.92+/-2.08 versus 2.71+/-4.75, respectively; p=0.068). Gastroduodenal toxicity was significantly lower with AZD3582 375 mg twice daily than with naproxen 250 mg twice daily (2.88+/-3.95 versus 6.16+/-9.36; p<0.05), and with AZD3582 750 mg twice daily versus naproxen 500 mg twice daily (3.08+/-2.80 versus 6.68+/-6.97; p<0.05). Equimolar twice-daily doses of AZD3582 and naproxen resulted in similar naproxen plasma levels and serum thromboxane B(2) inhibition.

CONCLUSIONS:

AZD3582 has an improved gastroduodenal safety profile compared with equimolar doses of naproxen. The gastroduodenal effects of AZD3582 375 mg and AZD3582 750 mg twice daily are similar. A once-daily regimen of AZD3582 might be less gastrotoxic than a twice-daily regimen.

PMID:
16497612
DOI:
10.1080/00365520510024197
[Indexed for MEDLINE]

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