Yeoh E K, Horowitz M, Russo A, Muecke T, Robb T, Chatterton B E
Department of Radiation Oncology, Royal Adelaide Hospital, South Australia.
Gut. 1993 Apr;34(4):476-82. doi: 10.1136/gut.34.4.476.
The effects of loperamide-N-oxide, a new peripheral opiate agonist precursor, on gastrointestinal function were evaluated in 18 patients with diarrhoea caused by chronic radiation enteritis. Each patient was given, in double-blind randomised order, loperamide-N-oxide (3 mg orally twice daily) and placebo for 14 days, separated by a washout period of 14 days. Gastrointestinal symptoms; absorption of bile acid, vitamin B12, lactose, and fat; gastric emptying; small intestinal and whole gut transit; and intestinal permeability were measured during placebo and loperamide-N-oxide phases. Data were compared with those obtained in 18 normal subjects. In the patients, in addition to an increased frequency of bowel actions (p < 0.001), there was reduced bile acid absorption, (p < 0.001) a higher prevalence of lactose malabsorption (p < 0.05) associated with a reduced dietary intake of dairy products (p < 0.02), and faster small intestinal (p < 0.001) and whole gut transit (p < 0.05) when compared with the normal subjects. There was no significant difference in gastric emptying between the two groups. Treatment with loperamide-N-oxide was associated with a reduced frequency of bowel actions (p < 0.001), slower small intestinal (p < 0.001), and total gut transit (p < 0.01), more rapid gastric emptying (p < 0.01), improved absorption of bile acid (p < 0.01), and increased permeability to 51Cr EDTA (p < 0.01). These observations indicate that: (1) diarrhoea caused by chronic radiation enteritis is associated with more rapid intestinal transit and a high prevalence of bile acid and lactose malabsorption, and (2) loperamide-N-oxide slows small intestinal transit, increases bile acid absorption, and is effective in the treatment of diarrhoea associated with chronic radiation enteritis.
对一种新型外周阿片类激动剂前体洛哌丁胺氮氧化物对18例慢性放射性肠炎所致腹泻患者胃肠功能的影响进行了评估。每位患者按双盲随机顺序接受洛哌丁胺氮氧化物（口服3毫克，每日两次）和安慰剂治疗14天，中间间隔14天的洗脱期。在安慰剂期和洛哌丁胺氮氧化物期测量胃肠症状、胆汁酸、维生素B12、乳糖和脂肪的吸收、胃排空、小肠和全肠道转运以及肠道通透性。将数据与18名正常受试者获得的数据进行比较。在患者中，除了排便频率增加（p<0.001）外，胆汁酸吸收减少（p<0.001），乳糖吸收不良的患病率更高（p<0.05），且与乳制品饮食摄入量减少有关（p<0.02），与正常受试者相比，小肠转运更快（p<0.001），全肠道转运更快（p<0.05）。两组之间胃排空无显著差异。洛哌丁胺氮氧化物治疗可使排便频率降低（p<0.001），小肠转运减慢（p<0.001），全肠道转运减慢（p<0.01），胃排空加快（p<0.01），胆汁酸吸收改善（p<0.01），对51Cr EDTA的通透性增加（p<0.01）。这些观察结果表明：（1）慢性放射性肠炎所致腹泻与肠道转运加快以及胆汁酸和乳糖吸收不良的高患病率有关；（2）洛哌丁胺氮氧化物可减慢小肠转运，增加胆汁酸吸收，对慢性放射性肠炎相关腹泻有效。
