Abstract

Intestinal permeability to polyethylene glycols (PEG) was measured simultaneously in jejunum and ileum of anesthetized rats. Using a mixture of PEG (400, 600 and 1000), which contained oligomers in the molecular weight (MW) range from 330 to 1122 Da, the MW permeability dependence of the rat small intestine was examined, employing an in situ recirculation perfusion technique. Individual oligomers of PEG were determined by HPLC with refractive index detection. Based on loss of oligomer from the reservoir, the permeabilities of the jejunum and ileum exhibited similar molecular weight dependencies. The apparent permeabilities were inversely proportional to ∼ MW2 in both jejunum and ileum (r = 0.99, P < 0.05). In the range studied, a distinct molecular weight cutoff was not identified at either site. Over the molecular weight range from 330 to 1122 Da (and corrected for the length of each segment) the apparent permeability (Papp) of PEG ranged from 29.54 ± 0.51 (mean ± SEM, n = 5) to 1.69 ± 0.08 µm/min in the jejunum, and from 18.97 ± 0.47 to 0.74 ± 0.05 µm/min in the ileum, indicating that the absorption of PEG oligomers is significantly greater in the jejunum than in the ileum (P < 0.05). A near constant ratio of jejunal/ileal permeabilities of 1.6 for the various oligomers (MW range from 330 to 990 Da) suggested that the major difference in the two sites is in the number, rather than the size distribution of the aqueous filled channels, possibly due to a difference in effective surface area for absorption.

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