Differential therapy of exocrine pancreatic insufficiency - Present status and future perspectives of pancreatic replacement therapy

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 exretion of more than 15 g per day, dyspeptic symptoms with strong meteorism, diarrhoea, and subjective malbehaviour 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-instabile 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 dosis 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.