Effect of cimetidine on enzyme inactivation, bile acid precipitation, and lipid solubilisation in pancreatic steatorrhoea due to cystic fibrosis.
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.
D000293:Adolescent; D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002446:Celiac Disease / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D011232:Chemical Precipitation; D002927:Cimetidine / Q000627:therapeutic use*; D003550:Cystic Fibrosis / Q000150:complications*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000378:metabolism; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D010179:Pancreas / Q000201:enzymology*; D010194:Pancreatin / Q000627:therapeutic use; D012995:Solubility; D014357:Trypsin / Q000378:metabolism
D001647:Bile Acids and Salts; D002927:Cimetidine; D010194:Pancreatin; D008049:Lipase; D014357:Trypsin