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World J Gastroenterol. Sep 7, 2014; 20(33): 11467-11485
Published online Sep 7, 2014. doi: 10.3748/wjg.v20.i33.11467
Pancreatic enzyme replacement therapy for pancreatic exocrine insufficiency in the 21st century
Tony Trang, Johanna Chan, David Y Graham
Tony Trang, Johanna Chan, David Y Graham, Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX 77030, United States
Author contributions: Trang T, Chan J and Graham DY have been involved equally and have read and approved the final manuscript; Trang T, Chan J and Graham DY meet the criteria for authorship established by the International Committee of Medical Journal Editors and verify the validity of the results reported.
Supported by The Office of Research and Development Medical Research Service Department of Veterans Affairs, Public Health Service grants No. DK067366 and No. DK56338 which funds the Texas Medical Center Digestive Diseases Center
Correspondence to: David Y Graham, MD, Professor, Department of Medicine, Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, 2002 Holcombe Blvd, Houston, TX 77030, United States. dgraham@bcm.edu
Telephone: +1-713-7950232 Fax: +1-713-7901040
Received: June 26, 2014
Revised: July 21, 2014
Accepted: July 29, 2014
Published online: September 7, 2014
Processing time: 72 Days and 23.9 Hours
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.

Keywords: Pancreatic insufficiency; Pancreatic enzyme replacement therapy; Lipase; Clinical trials; Steatorrhea; Fat malabsorption; Chronic pancreatitis

Core tip: In the last two decades, a number of studies comparing pancreatic enzymes and placebo have confirmed that pancreatic enzymes are superior to placebo for treatment of pancreatic malabsorption. While many patients achieved a satisfactory clinical response, individualization is often needed. Studies conclusively show that dose escalation is not a reliable method of obtaining further improvements and instead results in increased costs. Here, we describe alternate strategies for obtaining a satisfactory clinical response including changing to, or adding, a different product, adding non-enteric coated enzymes, use of antisecretory drugs and/or antacids, and changing the timing of enzyme administration.