生物学的同等性とバイオアベイラビリティのジャーナル

概要

Use of a Mutilumen Catheter to Assess the Bioavailability of an Enteric- Coated High-Buffered Pancrelipase Formulation in Patients with Exocrine Pancreatic Insufficiency

Ahsan N. Rizwan, Ryan Criste, Noelia Nebot, Kristina K. Wolf, Kim L. R. Brouwer and Lisa M. Gangarosa

Treatment of exocrine pancreatic insufficiency (EPI) secondary to conditions including cystic fibrosis or chronic pancreatitis requires exogenous supplementation with a specially formulated pancreatic enzyme product (PEP). The FDA has mandated that the intestinal bioavailability of these preparations be evaluated in vivo in patients. This pilot clinical study examined the feasibility of using a multi-lumen catheter with an occluding balloon to measure changes in intraduodenal enzyme concentrations following oral administration of a PEP. In this two arm cross-over study, patients with mild-severe EPI were administered enteric coated (EC) highbuffered pancrelipase or placebo capsules with a liquid Lundh meal. Gastric and duodenal samples were aspirated at 15-minute intervals over 3 hours in each treatment arm. The concentrations of three pancreatic enzymes (lipase, amylase, and protease) were measured in the collected fluids. The maximum concentration (Cmax), and area under the duodenal enzyme concentration vs. time profile (AUC) were determined. Comparison of enzyme concentrations between placebo and treatment phases demonstrated appreciable increases in all three enzymes in the subject with cystic fibrosis (CF+), but only a modest increase in the subject with mild-to-moderate EPI (CF-). During the EC-high-buffered pancrelipase+meal phase, the fold increase in the Cmax of lipase, amylase, and protease concentrations compared to the placebo+meal phase in subject CF- were 0.96, 1.65, and 1.64, respectively. In subject CF+, who had severe pancreatic enzyme insufficiency, the fold increase in the AUC of lipase, amylase and protease concentrations compared to the placebo+ meal phase was 66.1, 15.9, and 651, respectively. Time to peak concentration occurred earlier during the active treatment phase. In both subjects and both treatments a peak duodenal pH of 8 was measured. The catheter employed in this study can be used to determine bioavailability of PEPs in severe EPI in a single day pretreatment vs. post treatment setting (NCT00744250).