Stoltz Randall R, Harris Stuart I, Kuss Michael E, LeComte Diane, Talwalker Sheela, Dhadda Shobha, Hubbard Richard C
GI Associates, Evansville, Indiana, USA.
Am J Gastroenterol. 2002 Jan;97(1):65-71. doi: 10.1111/j.1572-0241.2002.05265.x.
The aim of this study was to compare the upper GI mucosal effects of i.v. parecoxib sodium with i.v. ketorolac tromethamine and placebo in healthy elderly subjects.
This was a two-center, double-blind, randomized, placebo-controlled study. Healthy subjects aged 65-75 yr who were shown at baseline endoscopy to have no gastric or duodenal lesions received either parecoxib sodium 40 mg b.i.d. for 7 days, ketorolac 15 mg q.i.d. for 5 days, or placebo for 7 days. Endoscopy was repeated at the end of dosing. Measures of upper GI effects were: 1) ulceration, 2) incidence of an ulcer and/or any erosions, and 3) incidence of an ulcer and/or > or = 11 erosions in the stomach, duodenum, or both.
No gastric or duodenal ulcers occurred in any subjects receiving parecoxib sodium (n = 29) or placebo (n = 32). In contrast, seven (23%) of the 31 ketorolac subjects had at least one ulcer; five (16%) had gastric ulcers, and two (6%) had duodenal ulcers (p < 0.05 vs parecoxib sodium and placebo for gastroduodenal ulcers and for gastric ulcers). A total of 28 (90%) ketorolac subjects had an ulcer or at least one erosion in the stomach, compared with incidences of four (14%) and two (6%) for parecoxib sodium and placebo, respectively. Incidences of duodenal ulcers/erosions were 45% (n = 14) for ketorolac, 10% (n = 3) for parecoxib sodium, and none for placebo. The differences between ketorolac and both other treatment groups were statistically significant for both stomach and duodenum. No parecoxib sodium or placebo subjects had an ulcer or > or = 11 erosions in the stomach, compared with eight (26%) ketorolac subjects (p < 0.05 vs both parecoxib sodium and placebo). No subject in any group had > or = 11 duodenal erosions.
These results indicate that multiple dose administration of parecoxib sodium is safe and well tolerated in healthy elderly subjects, with a decreased risk of gastroduodenal mucosal injury compared with ketorolac.
本研究旨在比较静脉注射帕瑞昔布钠、静脉注射酮咯酸氨丁三醇和安慰剂对健康老年受试者上消化道黏膜的影响。
这是一项双中心、双盲、随机、安慰剂对照研究。65 - 75岁的健康受试者在基线内镜检查时未发现胃或十二指肠病变，他们接受以下治疗之一：帕瑞昔布钠40 mg，每日两次，共7天；酮咯酸15 mg，每日四次，共5天；或安慰剂，共7天。给药结束时重复进行内镜检查。上消化道影响的测量指标为：1）溃疡；2）溃疡和/或任何糜烂的发生率；3）胃、十二指肠或两者中溃疡和/或≥11处糜烂的发生率。
接受帕瑞昔布钠（n = 29）或安慰剂（n = 32）的任何受试者均未发生胃或十二指肠溃疡。相比之下，31名酮咯酸受试者中有7名（23%）至少有一处溃疡；5名（16%）有胃溃疡，2名（6%）有十二指肠溃疡（与帕瑞昔布钠和安慰剂相比，胃十二指肠溃疡和胃溃疡的p < 0.05）。共有28名（90%）酮咯酸受试者胃内有溃疡或至少一处糜烂，相比之下，帕瑞昔布钠组和安慰剂组的发生率分别为4名（14%）和2名（6%）。十二指肠溃疡/糜烂的发生率在酮咯酸组为45%（n = 14），帕瑞昔布钠组为10%（n = 3），安慰剂组为零。酮咯酸与其他两个治疗组在胃和十二指肠方面的差异均具有统计学意义。与8名（26%）酮咯酸受试者相比，帕瑞昔布钠组或安慰剂组的任何受试者胃内均无溃疡或≥11处糜烂（与帕瑞昔布钠和安慰剂相比，p < 0.05）。任何组中均无受试者十二指肠糜烂≥11处。
这些结果表明，在健康老年受试者中多次给药帕瑞昔布钠是安全且耐受性良好的，与酮咯酸相比，胃十二指肠黏膜损伤风险降低。
