Bias Peter, Buchner Anton, Klesser Bernhard, Laufer Stefan
Pharos Contract Research, Ulm, Germany.
Am J Gastroenterol. 2004 Apr;99(4):611-8. doi: 10.1111/j.1572-0241.2004.04133.x.
Concerns exist over the safety of conventional nonsteroidal antiinflammatory drugs (NSAIDs) and selective cyclooxygenase (COX)-2 inhibitors. In experimental models, licofelone, a competitive inhibitor of 5-lipoxygenase (5-LOX) and COX-1/-2, has been shown to have good gastrointestinal and general tolerability and analgesic and antiinflammatory properties. The aim of the present endoscopy trial was to investigate the gastroduodenal tolerability of licofelone compared to placebo and naproxen in healthy volunteers.
In this randomized, parallel-group trial, healthy volunteers received licofelone 200 mg b.i.d. (n = 30), licofelone 400 mg b.i.d. (n = 30), naproxen 500 mg b.i.d. (n = 30), or placebo (n = 31). Tolerability was assessed by gastro/duodenoscopy following 4 wk of treatment. Laboratory parameters and the incidence of ulcers and adverse events were recorded.
Ulcers were observed in 20% of the naproxen-treated volunteers, compared with 0% of those receiving licofelone 200 mg, licofelone 400 mg, and placebo (p= 0.024). Posttreatment mean gastric Lanza scores were similar for volunteers who received placebo or either dose of licofelone, while Lanza scores were significantly worse following naproxen therapy (p < 0.00001). The gastric mucosa was normal in 93%, 89%, and 90% of volunteers who received licofelone 200 mg, licofelone 400 mg, or placebo, respectively, compared with 37% of volunteers receiving naproxen. The incidence of adverse events did not differ significantly between licofelone 200 mg or naproxen therapy. No clinically relevant changes in laboratory parameters were observed with licofelone or naproxen therapy.
The results from this trial indicate that licofelone has a potential gastrointestinal safety advantage over conventional NSAID therapy, as licofelone was associated with significantly superior gastric tolerability and a lower incidence of ulcers compared with naproxen in healthy volunteers. Further trials will be required to investigate the safety and efficacy of licofelone in the treatment of diseases such as osteoarthritis.
传统非甾体抗炎药（NSAIDs）和选择性环氧化酶（COX）-2抑制剂的安全性受到关注。在实验模型中，利考昔酮作为5-脂氧合酶（5-LOX）和COX-1/-2的竞争性抑制剂，已显示出良好的胃肠道耐受性和总体耐受性以及镇痛和抗炎特性。本内镜试验的目的是在健康志愿者中研究利考昔酮与安慰剂和萘普生相比的胃十二指肠耐受性。
在这项随机平行组试验中，健康志愿者分别接受每日两次200mg利考昔酮（n = 30）、每日两次400mg利考昔酮（n = 30）、每日两次500mg萘普生（n = 30）或安慰剂（n = 31）治疗。治疗4周后通过胃/十二指肠镜检查评估耐受性。记录实验室参数以及溃疡和不良事件的发生率。
在接受萘普生治疗的志愿者中，20%出现溃疡，而接受200mg利考昔酮、400mg利考昔酮和安慰剂的志愿者中这一比例为0%（p = 0.024）。接受安慰剂或任一剂量利考昔酮的志愿者治疗后的平均胃兰扎评分相似，而萘普生治疗后的兰扎评分明显更差（p < 0.00001）。接受200mg利考昔酮、400mg利考昔酮或安慰剂的志愿者中，分别有93%、89%和90%的胃黏膜正常，而接受萘普生的志愿者中这一比例为37%。200mg利考昔酮治疗组和萘普生治疗组的不良事件发生率无显著差异。利考昔酮或萘普生治疗后未观察到实验室参数有临床相关变化。
该试验结果表明，与传统NSAID治疗相比，利考昔酮具有潜在的胃肠道安全性优势，因为在健康志愿者中，利考昔酮的胃耐受性明显更好，溃疡发生率更低。需要进一步试验来研究利考昔酮治疗骨关节炎等疾病的安全性和有效性。
