Selective and Concentrative Enteropancreatic Recirculation of Antibiotics by Pigs

Abstract

Antibiotics that are efficacious for infectious pancreatitis are present in pancreatic exocrine secretion (PES) after intravenous administration and above minimal inhibitory concentrations. We measured concentrations of four antibiotics by tandem liquid chromatography–mass spectroscopy in plasma and PES after enteral administration to juvenile pigs with jugular catheters and re-entrant pancreatic-duodenal catheters. Nystatin, which is not absorbed by the intestine nor used for infectious pancreatitis (negative control), was not detected in plasma or PES. Concentrations of amoxicillin increased in plasma after administration (p = 0.035), but not in PES (p = 0.51). Metronidazole and enrofloxacin that are used for infectious pancreatitis increased in plasma after enteral administration and even more so in PES, with concentrations in PES averaging 3.1 (±0.5)- and 2.3 (±0.6)-fold higher than in plasma, respectively (p′s < 0.001). The increase in enrofloxacin in PES relative to plasma was lower after intramuscular administration (1.8 ± 0.5; p = 0.001). The present results demonstrate the presence of a selective and concentrative enteropancreatic pathway of secretion for some antibiotics. Unlike the regulated secretion of bile, the constitutive secretion of PES and intestinal reabsorption may provide a continuous exposure of pancreas tissue and the small intestine to recirculated antibiotics and potentially other therapeutic molecules. There is a need to better understand the enteropancreatic recirculation of antibiotics and the associated mechanisms.