Kahrilas P J
North-western University, Feinberg School of Medicine, Division of Gastroenterology, Chicago, IL 60611, USA.
Aliment Pharmacol Ther. 2004 Oct;20 Suppl 5:89-94; discussion 95-6. doi: 10.1111/j.1365-2036.2004.02135.x.
As the relative efficacy of therapeutic agents in the treatment of gastro-oesophageal reflux disease is related to how consistently and completely gastric acid secretion is suppressed, intragastric pH monitoring is a useful tool in stratifying therapies. If there is no acid in the stomach, there can be none to reflux into the oesophagus. Comparative crossover studies have shown consistently that once-daily esomeprazole (40 mg) provides more effective and longer lasting intragastric acid control than any other proton pump inhibitor currently available in healthy subjects and patients with gastro-oesophageal reflux disease. However, esomeprazole maintained intragastric pH > 4 for > or = 16 h in only about 55% of individuals tested. Thus, if more complete acid suppression is desirable, twice-daily proton pump inhibitor therapy may be advantageous. One such scenario is in patients with Barrett's metaplasia. Data from the ProGERD study suggest that, for each Los Angeles grade of oesophagitis, the healing rate for patients with Barrett's metaplasia is 10-30% less than that for non-Barrett's patients, being as low as 53% in patients with Los Angeles grade D oesophagitis. Also relevant to the Barrett's metaplasia population are studies on the oesophageal mucosa, which show that effective acid suppression favours differentiation and decreases epithelial cell proliferation. Both considerations argue for more intensive gastric acid inhibition than can be achieved with once-daily therapy, leading to experimentation with twice-daily proton pump inhibitor regimens. A randomized, double-blind, three-way crossover study compared esomeprazole 40 mg once daily with esomeprazole 20 mg and 40 mg twice daily and found that both twice-daily regimens were superior, maintaining intragastric pH > 4 for 73%[95% confidence interval (CI), 67-79%] and 80% (95% CI, 75-86%) of the day, respectively, compared with 59% (95% CI, 54-65%) of the day with esomeprazole 40 mg once daily, arguing that a twice-daily regimen may be the preferred strategy for patients with Barrett's metaplasia.
由于治疗药物在胃食管反流病治疗中的相对疗效与胃酸分泌被抑制的持续程度和完全程度相关，胃内pH监测是一种对治疗进行分层的有用工具。如果胃内没有酸，就不会有酸反流至食管。比较性交叉研究一致表明，对于健康受试者和胃食管反流病患者，每日一次服用埃索美拉唑（40毫克）比目前任何其他质子泵抑制剂能更有效且持久地控制胃内酸度。然而，在仅约55%的受试个体中，埃索美拉唑能使胃内pH值>4持续≥16小时。因此，如果需要更完全地抑制胃酸，每日两次服用质子泵抑制剂治疗可能更具优势。一种这样的情况见于患有巴雷特化生的患者。来自ProGERD研究的数据表明，对于洛杉矶分级的每一级食管炎，患有巴雷特化生的患者的愈合率比非巴雷特患者低10% - 30%，在洛杉矶D级食管炎患者中低至53%。与巴雷特化生人群相关的还有关于食管黏膜的研究，这些研究表明有效的胃酸抑制有利于分化并减少上皮细胞增殖。这两方面的考虑都表明需要比每日一次治疗更强化的胃酸抑制，从而引发了对每日两次质子泵抑制剂方案的试验。一项随机、双盲、三向交叉研究比较了每日一次服用40毫克埃索美拉唑与每日两次服用20毫克和40毫克埃索美拉唑，发现两种每日两次的方案都更具优势，分别使胃内pH值>4的时间占一天时间的73%[95%置信区间（CI），67 - 79%]和80%（95% CI，75 - 86%），而每日一次服用40毫克埃索美拉唑使胃内pH值>4的时间占一天时间的59%（95% CI，54 - 65%），这表明每日两次方案可能是患有巴雷特化生患者的首选策略。
Zotero 插件