Zentler-Munro P L, Fine D R, Batten J C, Northfield T C
Gut. 1985 Sep;26(9):892-901. doi: 10.1136/gut.26.9.892.
In pancreatic steatorrhoea, both pH-dependent bile acid precipitation and enzyme inactivation may limit the efficacy of pancreatic enzyme supplements and both may be preventable by addition of cimetidine. To separate these effects we compared postprandial jejunal aspirate from eight adults with steatorrhoea due to cystic fibrosis on three randomised treatment regimens (pancreatin, cimetidine, and both together). We also compared the results with those of previous studies of patients on no treatment, and of healthy subjects. On pancreatin 60% of the test meal entered the jejunum at pH less than 5 compared with 17% in health. Lipase concentration and lipolysis increased over the values on no treatment (14.2 vs 4.4 U/l, p less than 0.01; 16% vs 11%, p less than 0.02) but bile acid precipitation was not reduced (38% vs 27%, NS), and aqueous-phase lipid concentration decreased (6.7 vs 8.6 mM/l, p less than 0.05). On cimetidine, bile acid precipitation fell (19% vs 38%, p less than 0.05); although lipase concentration and lipolysis were lower than on pancreatin (4.8 U/l vs 14.2 U/l, p less than 0.01; 9% vs 16%, p less than 0.01) lipid solubilisation increased (8.8 vs 6.7 mM/l, p less than 0.05). On the combination, there was a marked improvement (p less than 0.02) in lipid solubilisation (18.3 mM/l), reflecting the improvement both in lipase (38.4 U/l) and lipolysis (24%), and in bile acid precipitation (5.6%). We conclude that the efficacy of pancreatin is limited by pH-dependent bile acid precipitation in addition to enzyme inactivation. The action of cimetidine in improving the efficacy of pancreatin depends on prevention of both these effects.
在胰腺性脂肪泻中，pH依赖性胆汁酸沉淀和酶失活均可能限制胰酶补充剂的疗效，而两者均可通过添加西咪替丁来预防。为了区分这些作用，我们比较了8名因囊性纤维化导致脂肪泻的成年人在三种随机治疗方案（胰酶、西咪替丁以及两者联合使用）下的餐后空肠抽吸物。我们还将结果与之前未接受治疗的患者以及健康受试者的研究结果进行了比较。服用胰酶时，60%的测试餐在pH值低于5时进入空肠，而健康状态下这一比例为17%。脂肪酶浓度和脂肪分解比未接受治疗时有所增加（14.2对4.4 U/L，p<0.01；16%对11%，p<0.02），但胆汁酸沉淀并未减少（38%对27%，无显著性差异），水相脂质浓度降低（6.7对8.6 mM/L，p<0.05）。服用西咪替丁时，胆汁酸沉淀减少（19%对38%，p<0.05）；尽管脂肪酶浓度和脂肪分解低于服用胰酶时（4.8 U/L对14.2 U/L，p<0.01；9%对16%，p<0.01），但脂质溶解增加（8.8对6.7 mM/L，p<0.05）。联合使用时，脂质溶解有显著改善（p<0.02）（18.3 mM/L），这反映出脂肪酶（38.4 U/L）和脂肪分解（24%）以及胆汁酸沉淀（5.6%）均有改善。我们得出结论，除酶失活外，胰酶的疗效还受pH依赖性胆汁酸沉淀的限制。西咪替丁提高胰酶疗效的作用取决于对这两种作用的预防。
