Spechler Stuart J, Sharma Prateek, Traxler Barry, Levine Douglas, Falk Gary W
Dallas Department of Veterans Affairs Medical Center, University of Texas Southwestern Medical Center, Dallas, Texas 75216, USA.
Am J Gastroenterol. 2006 Sep;101(9):1964-71. doi: 10.1111/j.1572-0241.2006.00661.x. Epub 2006 Jul 18.
It has been suggested that patients with Barrett's esophagus (BE) are unusually resistant to the antisecretory effects of proton pump inhibitors (PPIs).
To compare intragastric and intraesophageal acidity in patients with BE receiving esomeprazole 40 mg three times daily (t.i.d.), esomeprazole 40 mg twice daily (b.i.d.), and esomeprazole 20 mg t.i.d.
In this randomized, double-blind, three-way crossover study, patients with long-segment BE received each of the three esomeprazole dosages for 5 days separated by 10-14-day washout periods. Intragastric and intraesophageal pHs were measured for 24 h on day 5.
Among 31 patients with evaluable pH data, intragastric pH was >4.0 for 88.4%, 81.4%, and 80.4% of day 5 after treatment with esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. Esomeprazole 40 mg t.i.d. was significantly more effective than the other dosages (p < 0.01). Intraesophageal pH was <4.0 for mean values of <5% of the monitoring period with all the three dosing regimens, but esophageal pH remained <4.0 for >5% of the time in 16%, 23%, and 19% of patients receiving esomeprazole 40 mg t.i.d., 40 mg b.i.d., and 20 mg t.i.d., respectively. All dosages were well tolerated.
All the three esomeprazole dosages significantly decreased intragastric acidity and reduced esophageal acid exposure to mean normal values in the total group of patients with BE. However, abnormal esophageal acid exposure continued in 16-23% of patients despite the significant decrease in gastric acidity. These results suggest that the apparent "PPI resistance" described in patients with BE may be caused by their profound reflux diathesis rather than by gastric resistance to the antisecretory effects of PPIs.
有研究表明，巴雷特食管（BE）患者对质子泵抑制剂（PPI）的抑酸作用具有异常的抗性。
比较每日三次服用40毫克埃索美拉唑（t.i.d.）、每日两次服用40毫克埃索美拉唑（b.i.d.）以及每日三次服用20毫克埃索美拉唑的BE患者的胃内和食管内酸度。
在这项随机、双盲、三交叉研究中，长段BE患者接受三种埃索美拉唑剂量中的每一种治疗5天，中间间隔10 - 14天的洗脱期。在第5天测量胃内和食管内pH值24小时。
在31例有可评估pH数据的患者中，分别接受每日三次40毫克埃索美拉唑、每日两次40毫克埃索美拉唑和每日三次20毫克埃索美拉唑治疗后，第5天胃内pH值>4.0的时间分别占88.4%、81.4%和80.4%。每日三次服用40毫克埃索美拉唑比其他剂量显著更有效（p < 0.01）。在所有三种给药方案中，食管内pH值<4.0的平均值在监测期内均<5%，但在分别接受每日三次40毫克埃索美拉唑、每日两次40毫克埃索美拉唑和每日三次20毫克埃索美拉唑治疗的患者中，食管pH值在>5%的时间内仍<4.0的患者分别为16%、23%和19%。所有剂量的耐受性都良好。
在BE患者的总体人群中，所有三种埃索美拉唑剂量均显著降低了胃内酸度，并将食管酸暴露降低至平均正常值。然而，尽管胃酸度显著降低，但仍有16 - 23%的患者存在异常的食管酸暴露。这些结果表明，BE患者中描述的明显“PPI抗性”可能是由其严重的反流素质引起的，而不是胃对PPI抑酸作用的抗性。
