Pancreatic enzyme preparations

Treatment of chronic pancreatitis is aimed at removing the cause (ethanol abuse or biliary stones), providing analgesia, supplementing with pancreatic enzyme preparations, and implementing dietary restrictions. 

TABLE 20-3. Frequently Used Pancreatic Enzyme Preparations... 

A. Whitehead. Study to compare the enzyme activity, add resistance and dissolution characteristics of currently available pancreatic enzyme preparations. Pham. Weekt. 

M. One, H. Gutowsld, end T. Mackeniuth. in vitro testing of pancreatic enzyme preparations. In Pancreatic Enzymes in Health and Disease (P. Lonltisch, ed.). Springer, Bolin, 1991, pp. 65-70. 

Enzyme replacement therapy (ERT) is a therapeutic approach in which the specific enzyme that is absent or inactive in affected individuals is replaced with a functional enzyme molecule. Pancreatic enzyme preparations of porcine or bovine origin have been available in the United States for treatment of exocrine pancreatic insufficiency (EPI) in children and adults with cystic fibrosis and chronic pancreatitis since before the enactment of the Federal Food, Drug and Cosmetic Act of 1938 (ref FDA guidance on EIP April 2004). A... 

Q14 Pancreatic enzyme preparations contain amylase, lipase and protease enzymes. These supplements are given by mouth and compensate for the reduced or absent pancreatic secretions they assist the digestion of starch, fat and protein. Since the enzymes may be inactivated by gastric acid, they are usually presented in a protected, enteric-coated form which is sprinkled directly on the food. 

Malabsorption requires treatment when steatorrhea is documented (>7 g of fat in the feces per 24 hours while on a diet of 100 g/day of fat) and persistent weight loss occurs despite efforts to correct it. The combination of pancreatic enzymes (lipase, amylase, and protease) and a reduction in dietary fat (to <25 g/meal) enhances the patient s nutritional status and reduces (but does not totally correct) steatorrhea. The success of a pancreatic enzyme preparation requires that it contain a high concentration of lipase and proteases, be enteric-coated to avoid destruction by gastric acid, and be the... 

Thus the most important determinant in reducing steatorrhea is the total amount of active lipase that reaches the duodenum and empties with the meal. Generic pancreatic enzyme preparations have been associated with treatment failures when substituted for brand-name products. ... 

In general, pancreatic enzyme preparations are tolerated extremely well by patients. For patients with hypersensitivity to pork protein, bovine enzymes are available. Hyperuricosuria... 

Oral pancreatic enzyme supplements are available as powders, uncoated or coated tablets, capsules, enteric-coated spheres and microspheres, or enteric-coated microtablets encased in a cellulose or gelatin capsule (Table 28-2). Microencapsulated enteric-coated products are not superior to recommended doses of conventional non-enteric-coated enzyme preparations. The quantity of active lipase delivered to the duodenum appears to be a more important determinant in pancreatic enzyme replacement therapy than the dosage form. GI side effects appear to be dose related but occur less frequently with enteric-coated products. 

Enteric-coated pancreatic enzymes are more effective than regular formulations individual variations may require trials with several enzymatic preparations... 

Zaks and Klibanov (1984) discovered a new way of enzyme stabilization by enzyme dehydration. Dry pancreatic lipase, when placed in organic medium containing only 0.015% water, becomes much more stable than the normal enzyme preparation in an aqueous medium (see Chapter 9). 

Exocrine pancreatic insufficiency is most commonly caused by cystic fibrosis, chronic pancreatitis, or pancreatic resection. When secretion of pancreatic enzymes falls below 10% of normal, fat and protein digestion is impaired and can lead to steatorrhea, azotorrhea, vitamin malabsorption, and weight loss. Pancreatic enzyme supplements, which contain a mixture of amylase, lipase, and proteases, are the mainstay of treatment for pancreatic enzyme insufficiency. Two major types of preparations in use are pancreatin and pancrelipase. Pancreatin is an alcohol-derived extract of hog pancreas with relatively low concentrations of lipase and proteolytic enzymes, whereas pancrelipase is an enriched preparation. On a per-weight basis, pancrelipase has approximately 12 times the lipolytic activity and more than 4 times the proteolytic activity of pancreatin. Consequently, pancreatin is no longer in common clinical use. Only pancrelipase is discussed here. 

These agents are administered to aid in the digestion of food. The primary digestant preparations contain pancreatic enzymes or bile salts. Pancreatic enzymes such as amylase, trypsin, and lipase are responsible for digestion of carbohydrates, proteins, and lipids, respectively. These enzymes are normally synthesized in the pancreas and secreted into the duodenum via the pancreatic duct. Bile salts are synthesized in the liver, stored in the gallbladder, and released into the duodenum via the common bile duct. Bile salts serve to emulsify lipids in the intestinal tract and are important in lipid digestion and absorption. 

In addition to quantitative elementary analyses and qualitative reactions in all of which our pancreatic and malt amylase preparations show results typical of protein substances, we have submitted both of these amylase preparations to quantitative analysis with reference to the eight forms of nitrogen determinable by the VanSlyke method with results which show that the enzyme preparations yield all these products of hydrolysis in proportions within the range of variation shown by such typical protein... 

Therefore, another possibility in animal studies is to wash out the upper jejunum with a small volume of bicarbonate buffer, and use this fluid as a medium to determine the stability of a test macromolecule or formulation. A similar approach can be used to study enzyme activities in the colon in animals. It should be noted that the preparations should not be centrifuged, but used in their entirety as enzymes can bind to particulate matter or are on the surfaces of bacteria in the case of colon contents (Woodley 1991). Fluid thus obtained from the upper intestine should contain all the pancreatic enzymes, bile salts and sloughed-off cells, but again getting the concentrations right is not obvious. 

To restore nutrient digestion in exocrine pancreatic insufficiency, sufficient enzymatic activity must be administered into the duodenal lumen simultaneously with meal substrates. Intraluminal lipid digestion in postprandial chyme requires lipase activity of at least 40-60 IU/mL throughout the digestive period, which translates into 25,000 to 40,000 IU intraduodenal lipase for digestion of a regular meal. Because plain enzyme preparations undergo rapid lipase inactivation due to acid and proteolytic destruction, it is necessary to administer up to 10-fold more lipase orally to achieve these quantities within the duodenum. 

Q14 Cystic fibrosis patients are usually prescribed pancreatic enzymes to aid digestion. Which enzymes are likely to be included in these preparations ... 

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