1. Polyethylene glycol has been used extensively as a probe to measure passive small-intestinal permeability in viro. However, there has been some uncertainty as to its suitability for use as an indicator of the permeation of water-soluble molecules across the intestinal wall because it seems to traverse the mucosa in much greater quantities than sugar molecules of equivalent Mr.

2. We have measured the permeation of polyethylene glycol-400 and lactulose from aqueous solution across pure lipid solvents in vitro. We found considerable transport of polyethylene glycol-400 across chloroform (1.03 g h−1 m−2) but no movement across petroleum ether.

3. However, in a separate experiment in which phospholipid (egg lecithin) was dissolved in the petroleum ether, permeation of polyethylene glycol-400 did occur (0.13 g h−1 m2), implying interaction of polyethylene glycol-400 with the phospholipid. No permeation of lactulose was seen in any of the experiments.

4. Our results suggest that, because of its interaction with lipid solvents, polyethylene glycol-400 is unsuitable as a probe to measure passive intestinal permeability in vivo.

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