The indication for initiation of a replacement
therapy with pancreatic
enzymes in the course of ongoing
exocrine pancreatic insufficiency is clinically given with the appearance of loss of
body weight,
steatorrhea with stool fat excretion of more than 15 g per day, dyspeptic symptoms with strong meteorism, diarrhoea, and subjective misbehaviour caused by
chronic pancreatitis, in rare cases with the appearance of maldigestion of
proteins and
carbohydrates and--under certain circumstances--for the treatment of
pain in
chronic pancreatitis. Due to the increase of
chronic pancreatitis in recent years, the number of patients who necessarily have to be treated with
enzyme replacement therapy has increased, too. The adequate replacement
therapy with pancreatic
enzymes, especially in patients with severe
exocrine pancreatic insufficiency, is still a serious problem--requiring sufficient knowledge of the individual pathophysiological circumstances of the patient as well as the various pharmacological aspects of the different types of
enzyme drugs. The most important clinical aim of the replacement
therapy is the necessity to achieve a sufficient
lipase activity in the duodenum. Accordingly the achievement of this aim is the main problem in clinical practice, since the
acid-instable
lipase is predominantly inactivated by gastric acid and
proteases. Furthermore, in many cases an asynchronous gastroduodenal transport of the administered
enzyme drug and food is found as a result of inadequate size of the
drug or
drug particles. In general, the necessary doses of administered
enzymes does not follow general rules, but has to be adjusted individually. Recent scientific developments, as the characterization of an
acid-stable bacterial
lipase, the cloning of human
acid-stable
lipase, the transfection of human
lipase genes by virus-mediated gene transfer as well as the development of very small
acid-stable mini
microspheres, present interesting new perspectives to further optimize the efficacy of the
therapy of
exocrine pancreatic insufficiency in the near future.