Pancreatin preparations used in the treatment of cystic fibrosis--lipase content and in vitro release.
BACKGROUND
Pancreatic extracts are essential in the treatment of the majority of cystic fibrosis patients. The clinical response to different preparations is often unpredictable and at present there is no sure method of determining the best preparation for a particular patient.


METHODS
Creon, Nutrizym GR, Pancrease and the high-lipase versions, Creon 25,000, Nutrizym 22 and Pancrease HL, were investigated for lipase content and resistance to simulated gastric conditions. The rates of lipase release in response to pH change, bile salts and duodenal solids were investigated. The stability of lipase and its binding to duodenal solids were also investigated.


RESULTS
Declared values for lipase content were exceeded in all preparations. All preparations were acid resistant. The release of lipase in response to pH change showed notable differences in release rates. After 20 min at pH 5.5, Creon released three times the amount of lipase compared with Pancrease, the other preparations coming within the range. Above pH 5.75, the release rates were comparable amongst the preparations. Bile salts influenced release variably whilst release in a solid-rich duodenal fluid was much slower than in buffers. The released lipase was susceptible to proteolysis and pH-dependent binding to duodenal solids; these effects may compromise lipolysis.


CONCLUSIONS
These results show some factors contributing to variable clinical responses to pancreatic supplements. Improvements may result if a patient is assessed on different preparations.
Walters
M P
MP
Department of Chemical Pathology, St James's Hospital, NHS Trust, Leeds, UK.
Littlewood
J M
JM
D001647:Bile Acids and Salts / Q000737:chemistry; D001826:Body Fluids / Q000737:chemistry; D002021:Buffers; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004386:Duodenum / Q000737:chemistry; D005765:Gastrointestinal Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D008049:Lipase / Q000737:chemistry*; D010194:Pancreatin / Q000737:chemistry* / Q000493:pharmacokinetics*; D012995:Solubility; D014361:Trypsin Inhibitors / Q000737:chemistry
D001647:Bile Acids and Salts; D002021:Buffers; D005765:Gastrointestinal Agents; D014361:Trypsin Inhibitors; D010194:Pancreatin; D008049:Lipase