Lanza F, Schwartz H, Sahba B, Malaty H M, Musliner T, Reyes R, Quan H, Graham D Y
Houston Institute for Clinical Research, Texas 77074, USA.
Am J Gastroenterol. 2000 Nov;95(11):3112-7. doi: 10.1111/j.1572-0241.2000.03258.x.
The nitrogen-containing bisphosphonates alendronate and risedronate have been reported to have upper gastrointestinal (GI) safety and tolerability profiles comparable to those of placebo. Nevertheless, both agents have demonstrated similar potential for irritation of gastric mucosa at high doses in preclinical studies. The present study compared the potential for alendronate and risedronate to produce endoscopic upper GI mucosal irritation using the highest approved dosage regimens for the two agents.
This was a multicenter, randomized, parallel-group, double-blind, placebo-controlled trial in which a total of 235 patients (men or postmenopausal women, aged 45-80 yr) with normal upper GI endoscopy at baseline received 28-day treatments with the following: alendronate 40 mg/day (N = 90), risedronate 30 mg/day (N = 89), placebo (N = 36), or placebo with aspirin 650 mg q.i.d. for the last 7 days (N = 20). Endoscopy was repeated on day 29 using standardized scoring scales.
After 28 days of treatment, the alendronate and risedronate groups had comparable mean gastric and duodenal erosion scores that were significantly lower than those of the aspirin group. Esophageal scores were comparable in all groups. Gastric ulcers and/or large numbers of gastric erosions occurred in approximately 3% of alendronate and risedronate patients versus 60% with aspirin. Both bisphosphonates were clinically well tolerated.
The potential for gastroduodenal irritation is similar for alendronate and risedronate and is markedly less than for aspirin. The findings of this study, together with the large placebo-controlled clinical trial experience with both agents and extensive epidemiological data for alendronate, suggest that the risk for clinically important gastric irritation with these bisphosphonates is very low, even at the highest available doses.
据报道，含氮双膦酸盐阿仑膦酸钠和利塞膦酸钠的上消化道（GI）安全性和耐受性与安慰剂相当。然而，在临床前研究中，两种药物在高剂量时均显示出类似的胃黏膜刺激潜力。本研究使用两种药物的最高批准剂量方案，比较了阿仑膦酸钠和利塞膦酸钠引起内镜下上消化道黏膜刺激的可能性。
这是一项多中心、随机、平行组、双盲、安慰剂对照试验，共有235例基线时上消化道内镜检查正常的患者（男性或绝经后女性，年龄45 - 80岁）接受28天的治疗，治疗方案如下：阿仑膦酸钠40毫克/天（N = 90）、利塞膦酸钠30毫克/天（N = 89）、安慰剂（N = 36）或在最后7天服用含650毫克阿司匹林的安慰剂，每日4次（N = 20）。在第29天使用标准化评分量表重复进行内镜检查。
治疗28天后，阿仑膦酸钠组和利塞膦酸钠组的胃和十二指肠糜烂平均评分相当，且显著低于阿司匹林组。所有组的食管评分相当。约3%的阿仑膦酸钠和利塞膦酸钠患者出现胃溃疡和/或大量胃糜烂，而阿司匹林组为60%。两种双膦酸盐在临床上耐受性良好。
阿仑膦酸钠和利塞膦酸钠引起胃十二指肠刺激的可能性相似，且明显低于阿司匹林。本研究的结果，连同两种药物大量的安慰剂对照临床试验经验以及阿仑膦酸钠广泛的流行病学数据，表明即使使用最高可用剂量，这些双膦酸盐引起具有临床意义的胃刺激的风险也非常低。
