Effect of the administration schedule on the therapeutic efficacy of oral pancreatic enzyme supplements in patients with exocrine pancreatic insufficiency:: a randomized, three-way crossover study

Background: Oral pancreatic enzyme supplements should be properly administered in order to ensure an adequate gastric mixing with the food and simultameous gastric emptying with the chyme. Aim: To evaluate, in a prospective, randomized, open, comparative, three-way, crossover study, the effect of the administration schedule on the efficacy of oral pancreatic enzymes for the treatment of exocrine pancreatic insufficiency. Methods: Twenty-four consecutive chronic pancreatitis patients with maldigestion secondary to exocrine pancreatic insufficiency were treated with 40 000 U lipase in the form of capsules containing enteric-coated mini-microspheres. Capsules were taken just before meals (schedule A), just after meals (schedule B) or distributed along with meals (schedule C) for three consecutive 1-week crossover periods in a randomized order. Fat digestion before and during the three treatment periods was evaluated by an optimized mixed C-13-triglyceride breath test. Results: Before therapy, the (CO2)-C-13 recovery in the breath test was 23.8 +/- 15.8% (normal > 58.0%). During therapy, the (CO2)-C-13 recovery tended to be higher when capsules were taken along with meals ((CO2)-C-13 recovery 61.4 +/- 21.4%) or just after meals ((CO2)-C-13 recovery 60.6 +/- 21.8%) than when taken just before meals ((CO2)-C-13 recovery 53.9 +/- 20.3%). The percentage of patients who normalized fat digestion under therapy was 50, 54 and 63% with schedules A, B and C respectively. Conclusions: The efficacy of pancreatic enzyme supplements for the treatment of exocrine pancreatic insufficiency may be optimized by administration during or after meals.