Passage of molecules through the wall of the gastrointestinal tract. Intestinal permeability to polyethylene glycols in the 414- to 1,074-dalton range

Abstract

We describe the application of a simple and reliable experimental model for studying intestinal permeability. Swedish Landrace pigs were anesthetized and catheters put in the carotid artery, the external jugular vein, the proximal part of the duodenum, and the urinary bladder. A mixture of polyethylene glycols (PEGs) with molecular weights ranging from 414 to 1,074 daltons was then instilled into the duodenum and the urinary recovery of different-sized PEGs determined at time intervals using reversed-phase high-performance liquid chromatography. The recovery was inversely related to molecular size; after 4 h, 13.7% of the instilled amount of PEG 414 was recovered in the urine, whereas the corresponding value for PEG 1,074 was 0.34%. The presence of bile in the duodenum increased the recoveries of all PEGs: corresponding values for PEG 414 and 1,074 were then 28.3 and 0.79%, respectively. These data indicate that (i) intestinal permeability to PEGs in the 414- to 1,074-dalton range can be studied in a quantitative, yet simple way using a pig experimental model, and (ii) the presence of bile in the duodenum considerably increases the intestinal absorption of 414- to 1,074-dalton PEGs. The possibility that bile interacts with PEGs much the same as with hydrophobic and amphiphilic compounds is discussed.