Pancrelipase, USP contains lipase, protease and amylase obtained from porcine pancreas. Normal pancreatic function includes secretion of proteolytic enzymes such as proteases (trypsin and chymotrypsin), nonproteolytic enzymes such as lipase and amylase, and electrolytes such as bicarbonate, chloride, sodium and potassium. Lipase, protease and amylase break down fat, protein, and starches, respectively, in the small intestine. Lipase hydrolyzes fats into glycerol and fatty acids. Protease converts proteins into proteoses and derived substances, while amylase converts starches into dextrins and sugars. Pancreatic enzymes are used to correct maldigestion, malabsorption and pain associated with pancreatic insufficiency. The major maldigestion/malabsorption problems arise from incomplete fat digestion. Exogenous pancrelipase reduces the amount of nitrogen and fat excreted in the stool. Activity of these products are dependent upon the amount of pancrelipase delivered to the small intestine. This delivery can be hampered by inactivation from low gastric pH, acidic precipitation of bile salts, and the proteolytic activity of the component protease. Pancreatic enzymes are more active at pH greater than 4, with lipase being the most sensitive of the pancreatic enzymes to inactivation by low pH. Malabsorption of fat is likely if an individual, ingesting 100 gm of fat per day, excretes more than 7 gm of fat (or 18 mmol) in a 24-hour period. Malabsorption of protein is likely if nitrogen excretion is greater than 2.5 gm per 24-hours (16% of protein by weight is nitrogen). In order for fat maldigestion to occur, a pancreas must secrete less than 10% of its normal output.

The enzymes contained in COTAZYM® (pancrelipase capsules, USP) are not absorbed systemically; therefore, pharmacokinetic studies of their absorption, distribution, metabolism, and excretion have not been conducted. The contents of COTAZYM® capsules are released in the stomach, whereupon some of the enzyme is inactivated by acid. The remaining enzymes traverse into the duodenum, where they facilitate digestion and subsequently are hydrolyzed to their constituent amino acids by proteases. Pancreatic extracts contain purines which are absorbed into the general circulation and are converted to uric acid. This uric acid could lead to hyperurticemia, hyperuticosuria, and possible kidney damage. Chymotrypsin activity in the stool is indicative of exocrine pancreatic function. Ingestion of pancrelipase enzymes result in an increase in chymotrypsin in the stool.

Clinical bioactivity and bioavaliability studies in patients with exocrine pancreatic insufficiency from cystic fibrosis or chronic alcoholic pancreatitis have shown that the enzymes from COTAZYM® are released at the duodenojejunal junction.

A study was conducted in 6 patients (ages 43-58) with pancrelipase insufficiency secondary to chronic alcoholic pancreatitis. Four of the patients received 4 capsules of COTAZYM® with a standard test meal. The mean (±SEM) percent of ingested dose of lipase and trypsin delivered to the duodenum postprandially was 15.1% (±2.1) and 11.3% (±1.6), respectively. A randomized 3-way crossover study was also performed on this group of patients to further ascertain bioavaliability. Each patient received 10 PANCREATIN® tablets per meal, 4 COTAZYM® capsules per meal, and 4 or 8 PANCREASE® capsules per meal in a randomized order. In patients who received COTAZYM®, PANCREASE®, or PANCREATIN® while on a 100 gm fat/day diet, the fat excretions were 15.0 gm, 13.0 gm, and 19.0 gm per 24 hours, respectively, while fat excretion was 31.0 gm/24 hours in the no enzyme treatment group. ¹ An investigation was also conducted in 8 cystic fibrosis patients (ages 18-29) with steatorrhea who were already on some type of enzyme replacement therapy. Two patients were given a test meal together with 4 capsules of COTAZYM®. The mean delivery of lipase and trypsin to the duodenum postprandially was 7.6% (3.5-11.7%) and 14.5% (12-17%) of intake, respectively. A randomized 2-way crossover study was performed on 7 of these 8 patients. Each patient received 4 COTAZYM® capsules per meal or 8 PANCREASE® capsules per meal, while on a 100 gm fat/day diet. Steatorrhea was controlled with 19.2% of fat excreted (as % of fat intake) for COTAZYM® and 5.9% of fat excreted for PANCREASE®, reduced from 28% fat excreted with previous treatments. ²

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