Intestinal absorption of sugar-coupled somatostatin analogs

The intestinal absorption of glycosylated somatostatin analogs was compared in rat enterocyte brush border membranes as an in vitro test system and rats as an in situ absorption model. Derivatives of the cyclic octapeptide octreotide with mono-, di-, and trisaccharide residues were used. The uptake of octreotide by the vesicles was inhibited by the glycosylated analogs. The uptake was not inhibited by the bicyclic octapeptide alpha-amanitin, which exhibits structural similarity but is not absorbed in rats. The inhibition of octreotide permeation into the vesicles decreased in the presence of derivatives with an increasing length of the carbohydrate residues. To evaluate, whether the vesicle system is predictable for the in situ situation, the extent of absorption of the peptides was determined after intrajejunal administration. A linear relationship between inhibitory capacity of the octreotide derivatives in the vesicle system and their in situ absorption efficiency was found when blood was taken from a mesenteric vein. However, after sampling from a peripheral vein, deviations from the predicted values were noted. These differences reflected changes in pharmacokinetics (e.g., hepatic elimination) rather than in absorption. In summary, the data indicate that the vesicle system is a useful tool to predict the absorption efficiency of glycosylated somatostatin analogs in situ.