Lanza F L, Codispoti J R, Nelson E B
Houston Institute of Clinical Research, Texas 77074, USA.
Am J Gastroenterol. 1998 Jul;93(7):1051-4. doi: 10.1111/j.1572-0241.1998.00327.x.
The objective of this study was to endoscopically assess in healthy subjects the gastrointestinal effects of over-the-counter (OTC) doses of ketoprofen. Ketoprofen is a potent nonsteroidal antiinflammatory agent (NSAID) recently approved for OTC use as an analgesic/antipyretic at doses of 75 mg versus the usual dose of < or = 300 mg daily. In epidemiological studies, ketoprofen at prescription doses has consistently been in the higher relative risk group of NSAIDs in the occurrence of gastrointestinal complications of therapy. The gastrointestinal effects of the OTC (US) dose of ketoprofen have not been reported.
In a randomized, double blind, three way crossover study, 24 healthy subjects received 7 days of therapy with ketoprofen 75 mg/day, acetaminophen 4000 mg/day, and placebo. Gastroduodenal endoscopy was performed before and at the end of each treatment period. The condition of the mucosa was graded compositely for the gastric antrum, fundus, body, and duodenum.
Significantly more frequent and severe gastric mucosal injury was observed after dosing with ketoprofen compared with acetaminophen (p = 0.0001). The acetaminophen group showed no difference from placebo (p = 0.8783). Two subjects developed frank gastric ulcers with ketoprofen therapy. Marginally more frequent (p = 0.0703) and significantly more severe (p = 0.0117) duodenal mucosal injury was seen. No significant differences were observed between treatment groups with respect to subjective symptoms of gastric discomfort or adverse events.
These results indicate that even at lower (OTC) doses (75 mg/day) ketoprofen is associated with significant gastrointestinal irritation.
本研究的目的是通过内镜评估非处方(OTC)剂量的酮洛芬对健康受试者胃肠道的影响。酮洛芬是一种强效非甾体抗炎药(NSAID),最近被批准作为镇痛药/退热药以75mg的OTC剂量使用,而其通常剂量为每日≤300mg。在流行病学研究中,处方剂量的酮洛芬在NSAID治疗引起胃肠道并发症的相对风险方面一直处于较高组。尚未有关于酮洛芬OTC(美国)剂量胃肠道影响的报道。
在一项随机、双盲、三交叉研究中,24名健康受试者接受了为期7天的治疗,分别为每日75mg酮洛芬、每日4000mg对乙酰氨基酚和安慰剂。在每个治疗期开始前和结束时进行胃十二指肠内镜检查。对胃窦、胃底、胃体和十二指肠的黏膜状况进行综合分级。
与对乙酰氨基酚相比,服用酮洛芬后观察到胃黏膜损伤的频率和严重程度显著更高(p = 0.0001)。对乙酰氨基酚组与安慰剂组无差异(p = 0.8783)。两名受试者在接受酮洛芬治疗时出现了明显的胃溃疡。十二指肠黏膜损伤略更频繁(p = 0.0703)且显著更严重(p = 0.0117)。各治疗组在胃部不适主观症状或不良事件方面未观察到显著差异。
这些结果表明,即使是较低的(OTC)剂量(75mg/天),酮洛芬也会引起明显的胃肠道刺激。