The effect of amiloride on the in vivo effective permeability of amoxicillin in human jejunum:: experience from a regional perfusion technique

The purpose of this human intestinal perfusion study (in vivo) was twofold. Firstly, we aimed to determine the effective in vivo jejunal permeability (P-eff) of arnoxicillin and to classify it according to the Biopharmaceutics Classification System (BCS). Secondly, we investigated the acute effect of amiloride on the jejunal P-eff of arnoxicillin. Amoxicillin, a beta-lactam antibiotic, has been reported to be absorbed across the intestinal mucosa by both passive diffusion and active transport. A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut((R)) perfusion tube in 14 healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods of 100 min each. The concentration of amoxicillin entering the jejunal segment was 300 mg/l in both periods, and amiloride, an inhibitor of the Na+/H+ exchanger, was added at 25 mg/l in period 2. The concentrations of amoxicillin and amiloride in the outlet jejunal perfusate were measured with two different HPLC-methods. Antipyrine and [C-14]PEG 4000 were added as internal standards to the perfusion solution. Amiloride had no significant effect on the jejunal P-eff of amoxicillin. The human in vivo jejunal P-eff for amoxicillin was 0.34 +/- 0.11 X 10(-4) and 0.46 +/- 0.12 X 10(-4) cm/s in periods 1 and 2, respectively. The high jejunal P-eff for amiloride was 1.63 +/- 0.51 X 10(-4) cm/s which predicts an intestinal absorption of more than 90%. Following the BCS amoxicillin was classified as a low P-eff drug, and amiloride had no acute effect on the in vivo jejunal P-eff of amoxicillin. (C) 2002 Elsevier Science B.V. All rights reserved.