Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21^stcentury

Abstract

Restitution of normal fat absorption in exocrine pancreatic insufficiency remains an elusive goal. Although many patients achieve satisfactory clinical results with enzyme therapy, few experience normalization of fat absorption, and many, if not most, will require individualized therapy. Increasing the quantity of lipase administered rarely eliminates steatorrhea but increases the cost of therapy. Enteric coated enzyme microbead formulations tend to separate from nutrients in the stomach precluding coordinated emptying of enzymes and nutrients. Unprotected enzymes mix well and empty with nutrients but are inactivated at pH 4 or below. We describe approaches for improving the results of enzyme therapy including changing to, or adding, a different product, adding non-enteric coated enzymes, (e.g., giving unprotected enzymes at the start of the meal and acid-protected formulations later), use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration. Because considerable lipid is emptied in the first postprandial hour, it is prudent to start therapy with enteric coated microbead prior to the meal so that some enzymes are available during that first hour. Patients with hyperacidity may benefit from adjuvant antisecretory therapy to reduce the duodenal acid load and possibly also sodium bicarbonate to prevent duodenal acidity. Comparative studies of clinical effectiveness of different formulations as well as the characteristics of dispersion, emptying, and dissolution of enteric-coated microspheres of different diameter and density are needed; many such studies have been completed but not yet made public. We discuss the history of pancreatic enzyme therapy and describe current use of modern preparations, approaches to overcoming unsatisfactory clinical responses, as well as studies needed to be able to provide reliably effective therapy.

Use of an In‐line Digestive Cartridge With Enteral Nutrition Improves the Weight Trajectory of 2 Children With Cystic Fibrosis Complicated by Another Medical Diagnosis

“…Even when pancreatic enzymes are delivered to the GI tract, either orally or through a feeding tube, their effectiveness depends on several factors. Gastric motility, bicarbonate release, intestinal pH, and dosing can all influence the performance of enzyme therapy . If these factors are not synchronized physiologically, the pancrelipase can be ineffective.…”

“…If these factors are not synchronized physiologically, the pancrelipase can be ineffective. Trang and colleagues reviewed the current literature concerning the use of PERT for pancreatic insufficiency. To meet FDA standards, the manufacturers tested the dissolution characteristics of enzyme microspheres in vitro.…”

“…To meet FDA standards, the manufacturers tested the dissolution characteristics of enzyme microspheres in vitro. However, published data describing the dissolution of microspheres in vivo are not available . Enzyme microsphere activity peaks at 30 minutes and diminishes over 2 hours .…”

“…Encapsulated pancrelipase products contain enteric‐coated enzyme microspheres designed to dissolve in the small intestine and begin nutrient digestion . These microspheres require a pH of 5.5–6.0 to be effective . In CF, a lack of bicarbonate release from the pancreas may prevent adequate neutralization of pH in the duodenum.…”

“…[13][14][15]17 These microspheres require a pH of 5.5-6.0 to be effective. 1,18 In CF, a lack of bicarbonate release from the pancreas may prevent adequate neutralization of pH in the duodenum. As a result, enzyme microspheres may not dissolve until they reach distal portions of the GI tract, leaving some macronutrients undigested or causing them to miss crucial absorptive surfaces.…”