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A randomized, double-blind, crossover comparative endoscopy study on the gastroduodenal tolerability of a highly
I Bjarnason1, A Macpherson, H Rotman
1Dept. of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, UK.
Background:
Inhibition of constitutively expressed cyclooxygenase (Cox-1) is thought to play an important role in the gastrointestinal toxicity of nonsteroidal anti-inflammatory drugs (NSAID), while their therapeutic action may be due to inhibition of the enzyme Cox-2, which is specifically expressed at sites of inflammation. NSAIDs with high affinity and specifity for Cox-2 hold the promise of maintaining efficacy without the gastrointestinal side effects of conventional NSAIDs.
Methods:
We assessed the gastrointestinal tolerability of flosulide (20 mg twice a day), a highly selective Cox-2 inhibitor with that of naproxen (500 mg twice a day), which has equal affinity for Cox-1 and -2 in 19 patients with osteoarthrosis in a randomized, double blind, crossover endoscopy study. Subjects were treated for 2 weeks with a 2-week washout period. Gastroduodenal damage was primarily assessed as by Lanza (grades 0-4).
Results:
No stomach damage was seen in 13 (68%) patients after flosulide and in 5 (37%) after naproxen (P < 0.001). Lanza scores were significantly lower after flosulide (0.58) than after naproxen (1.47) (P < 0.001; odds ratio, 84.4; 95% confidence interval, 1.45-4908). Flosulide was significantly better tolerated (P < 0.005) than naproxen.
Conclusion:
These results endorse the idea that highly selective Cox-2 inhibitors may be associated with lesser gastrointestinal side effects than conventional NSAIDs.
Insights
Highly selective cyclooxygenase-2 (Cox-2) inhibitors like flosulide may offer reduced gastrointestinal side effects compared to conventional nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen, according to a clinical study.
Area of Science:
- Pharmacology
- Gastroenterology
- Clinical Medicine
Background:
- Nonsteroidal anti-inflammatory drugs (NSAIDs) can cause gastrointestinal toxicity due to cyclooxygenase-1 (Cox-1) inhibition.
- Therapeutic effects of NSAIDs are linked to Cox-2 inhibition at inflammatory sites.
- Selective Cox-2 inhibitors offer potential for efficacy without gastrointestinal side effects.
Purpose of the Study:
- To compare the gastrointestinal tolerability of a selective Cox-2 inhibitor, flosulide, with a non-selective NSAID, naproxen.
- To evaluate the safety profile of flosulide in patients with osteoarthrosis.
Main Methods:
- A randomized, double-blind, crossover endoscopy study was conducted.
- 19 patients with osteoarthrosis received flosulide (20 mg twice daily) or naproxen (500 mg twice daily) for 2 weeks, followed by a 2-week washout period.
- Gastroduodenal damage was assessed using the Lanza score (grades 0-4).
Main Results:
- Significantly fewer patients experienced stomach damage with flosulide (68%) compared to naproxen (37%) (P < 0.001).
- Lanza scores were substantially lower for flosulide (0.58) than for naproxen (1.47) (P < 0.001).
- Flosulide demonstrated significantly better gastrointestinal tolerability than naproxen (P < 0.005).
Conclusions:
- Highly selective Cox-2 inhibitors are associated with fewer gastrointestinal side effects than conventional NSAIDs.
- Flosulide shows promise as a safer alternative for managing osteoarthrosis pain.
- Targeting Cox-2 selectively may mitigate NSAID-induced gastroduodenal damage.