Scheiman James M, Cryer Byron, Kimmey Michael B, Rothstein Richard I, Riff Dennis S, Wolfe Michael M
Department of Internal Medicine, University of Michigan, Ann Arbor, 48109-0362, USA.
Clin Gastroenterol Hepatol. 2004 Apr;2(4):290-5. doi: 10.1016/s1542-3565(04)00057-6.
BACKGROUND & AIMS: Ibuprofen is a well-tolerated nonsteroidal anti-inflammatory drug (NSAID), particularly at over-the-counter (OTC) doses. Cyclooxygenase 2 (COX-2)-selective inhibitors cause less ulceration than prescription-dose nonselective NSAIDs. We compared endoscopic injury related to nonprescription ibuprofen doses with celecoxib, also comparing prescription doses of naproxen with placebo as a positive control.
The study was a randomized, placebo-controlled, double blind, double-dummy endoscopic evaluation with concealed allocation. A 2-way crossover with a 4-5-week washout period was used. Participants were healthy adults with normal baseline findings from endoscopy. Ninety-five subjects were randomly assigned, and 79 subjects completed both study phases. Age distribution was reflective of the target population of the OTC agent. Twenty percent were infected with Helicobacter pylori, and 79% and 67% had a current or past medical problem, respectively. Qualifying subjects, stratified by the presence or absence of H. pylori infection (n = 20), were randomly assigned to 1 of the 4 sequences (phase I/II) as follows: ibuprofen/celecoxib; celecoxib/ibuprofen, naproxen/placebo, or placebo/naproxen. Primary end points were the frequency of endoscopic ulcers and erosions in the groups administered: (1) celecoxib vs. ibuprofen and (2) naproxen vs. placebo.
In celecoxib-treated subjects, 2.6% developed ulcers compared with 17.9% of those treated with ibuprofen (P = 0.056). Naproxen treatment was associated with a significantly greater ulceration rate compared with placebo.
Short-term use of the nonselective COX inhibitors ibuprofen and naproxen is associated with a greater risk for endoscopic mucosal injury compared with the COX-2-selective inhibitor celecoxib or placebo. A prospective analysis appropriately powered to address the incidence of clinically significant gastroduodenal ulceration associated with the short-term use of these agents would be required to further define the clinical relevance of these findings.
布洛芬是一种耐受性良好的非甾体抗炎药（NSAID），尤其是非处方（OTC）剂量时。环氧化酶2（COX-2）选择性抑制剂引起的溃疡比处方剂量的非选择性NSAID少。我们比较了非处方剂量布洛芬与塞来昔布相关的内镜损伤，同时将萘普生的处方剂量与安慰剂作为阳性对照进行比较。
本研究是一项采用隐匿分配的随机、安慰剂对照、双盲、双模拟内镜评估。采用为期4 - 5周洗脱期的双向交叉设计。参与者为内镜检查基线结果正常的健康成年人。95名受试者被随机分配，79名受试者完成了两个研究阶段。年龄分布反映了OTC药物的目标人群。20%的受试者感染幽门螺杆菌，79%和67%的受试者分别有当前或既往病史。符合条件的受试者按是否感染幽门螺杆菌（n = 20）分层，随机分配到以下4个序列（I/II期）中的1个：布洛芬/塞来昔布；塞来昔布/布洛芬、萘普生/安慰剂或安慰剂/萘普生。主要终点是给药组内镜下溃疡和糜烂的发生率：（1）塞来昔布与布洛芬；（2）萘普生与安慰剂。
塞来昔布治疗的受试者中，2.6%发生溃疡，而布洛芬治疗的受试者中这一比例为17.9%（P = 0.056）。与安慰剂相比，萘普生治疗的溃疡发生率显著更高。
与COX-2选择性抑制剂塞来昔布或安慰剂相比，非选择性COX抑制剂布洛芬和萘普生的短期使用与内镜下黏膜损伤风险更高相关。需要进行一项有足够效力的前瞻性分析来确定这些药物短期使用相关的临床显著胃十二指肠溃疡的发生率，以进一步明确这些发现的临床相关性。
