Pancreatic enzymes and fibrosing colonopathy

Abstract

We agree with C J Powell's conclusion1Powell CJ Colonic toxicity from pancreatins: a contemporary safety issue.Lancet. 1999; 353: 911-915Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar that the abnormal gastrointestinal tract in cystic fibrosis is the most likely mechanism involved in the pathogenesis of pancreatic-enzyme-induced colonopathy. We postulated that the increased intestinal permeability of patients with cystic fibrosis was involved2Lloyd-Still JD Cystic fibrosis and colonic strictures. A new iatrogenic disease.J Clin Gastroenterol. 1995; 21: 2-5Crossref PubMed Scopus (24) Google Scholar and used a rat model to investigate this possibility.3Lloyd-Still JD Uhing MR Arango V Fusaro A Kimura RE The effect of intestinal permeability on pancreatic enzyme induced enteropathy in the rat.J Pediatr Gastroenterol Nutr. 1998; 26: 489-495Crossref PubMed Scopus (14) Google Scholar Despite an infusion of pancreatic enzymes for up to 56 days, we were unable to induce intestinal damage in this model unless intestinal permeability was increased by agents such as oleic acid, reserpine, or non-steroidal anti-inflammatory drugs. We have shown noticeable synergism between the indometacin-treated rat and doses of Eudragit-containing enzymes (150 000 U lipase/kg4Kimura RE Arango V Lloyd-Still JD Indomethacin and pancreatic enzymes synergistically damage intestine of rats.Dig Dis Sci. 1998; 43: 2322-2332Crossref PubMed Scopus (9) Google Scholar) and with ibuprofen and non-Eudragit enzymes (10 000 and 40 000 U lipase/kg5Kimura RE, Dy SAD, Uhing MR, Beno DWA, Jiyamapa VA, Lloyd-Still JD. The effects of high dose ibuprofen and pancreatic enzymes on the intestine of the rat. J Pediatr Gastroenterol Nutr (in press).Google Scholar). Not only is there damage to the intestine, but there is damage to the liver in both animals and the man. We used the same model to infuse Eudragit via duodenal catheter for 10 days at 50, 100, and 200 mg per day, and were unable to confirm van Velzen's findings in the pig caecum (unpublished data). We have also reported pancreatic-enzyme-induced colonopathy in a patient without cystic fibrosis who had coeliac disease (also characterised by increased intestinal permeability).*Data available from author, on request, courtesy of the Committee on the Safety of Medicines. We agree with C J Powell's conclusion1Powell CJ Colonic toxicity from pancreatins: a contemporary safety issue.Lancet. 1999; 353: 911-915Summary Full Text Full Text PDF PubMed Scopus (14) Google Scholar that the abnormal gastrointestinal tract in cystic fibrosis is the most likely mechanism involved in the pathogenesis of pancreatic-enzyme-induced colonopathy. We postulated that the increased intestinal permeability of patients with cystic fibrosis was involved2Lloyd-Still JD Cystic fibrosis and colonic strictures. A new iatrogenic disease.J Clin Gastroenterol. 1995; 21: 2-5Crossref PubMed Scopus (24) Google Scholar and used a rat model to investigate this possibility.3Lloyd-Still JD Uhing MR Arango V Fusaro A Kimura RE The effect of intestinal permeability on pancreatic enzyme induced enteropathy in the rat.J Pediatr Gastroenterol Nutr. 1998; 26: 489-495Crossref PubMed Scopus (14) Google Scholar Despite an infusion of pancreatic enzymes for up to 56 days, we were unable to induce intestinal damage in this model unless intestinal permeability was increased by agents such as oleic acid, reserpine, or non-steroidal anti-inflammatory drugs. We have shown noticeable synergism between the indometacin-treated rat and doses of Eudragit-containing enzymes (150 000 U lipase/kg4Kimura RE Arango V Lloyd-Still JD Indomethacin and pancreatic enzymes synergistically damage intestine of rats.Dig Dis Sci. 1998; 43: 2322-2332Crossref PubMed Scopus (9) Google Scholar) and with ibuprofen and non-Eudragit enzymes (10 000 and 40 000 U lipase/kg5Kimura RE, Dy SAD, Uhing MR, Beno DWA, Jiyamapa VA, Lloyd-Still JD. The effects of high dose ibuprofen and pancreatic enzymes on the intestine of the rat. J Pediatr Gastroenterol Nutr (in press).Google Scholar). Not only is there damage to the intestine, but there is damage to the liver in both animals and the man. We used the same model to infuse Eudragit via duodenal catheter for 10 days at 50, 100, and 200 mg per day, and were unable to confirm van Velzen's findings in the pig caecum (unpublished data). We have also reported pancreatic-enzyme-induced colonopathy in a patient without cystic fibrosis who had coeliac disease (also characterised by increased intestinal permeability). *Data available from author, on request, courtesy of the Committee on the Safety of Medicines.