Polyethylene glycol 400 penetration of the colonic epithelial barrier of the rat

Permeability changes of polyethylene glycol 400 have been seen in patients with inflammatory bowel diseases. Because the colon can be involved in inflammatory bowel disease, the mechanisms, kinetics, and influence of intraluminal factors on polyethylene glycol 400 permeation of perfused colonic segments of rats were studied. The absorption rate of polyethylene glycol 400 was linearly related to its luminal concentration (r = 0.94), suggesting that passive diffusion is a significant mechanism involved in polyethylene glycol 400 absorption. Changing the perfusate pH from 6.0 to 7.5 did not affect water absorption or polyethylene glycol 400 permeation. Increasing luminal osmolarity significantly decreased water and polyethylene glycol 400 absorption (P < 0.01). The relationship between polyethylene glycol 400 and water absorption at different luminal osmolarities was linear (r = 0.97). At luminal osmolarity of 0.3 osm/L, 14.3% of polyethylene glycol 400 absorption was mediated by passive diffusion and 85.7% was mediated by convection. The solvent drag reflection coefficient for polyethylene glycol 400 in the colon was 0.03. Taurocholic acid (10 mmol/L) and chenodeoxycholic acid (5 mmol/L) decreased polyethylene glycol 400 and water absorption (P < 0.01). Addition of 1 μg/mL of 16,16,-dimethyl prostaglandin E₂, 2 mmol/L of dibutyryladenosine-3′,5′-cyclic monophosphate, or 10 mmol/L of aminophylline significantly decreased water and polyethylene glycol 400 absorption (P < 0.01). These studies demonstrate that polyethylene glycol 400 permeation of the colon is mediated by both passive diffusion and solvent drag. Convective absorption is the major mechanism of polyethylene glycol 400 permeation of the colon. Polyethylene glycol 400 permeation is modified by bile acids, prostaglandins, and cyclic nucleotides through changes in water flux.