INTESTINAL-ABSORPTION OF SUGAR-COUPLED SOMATOSTATIN ANALOGS

The intestinal absorption of glycosylated somatostatin analogs was com pared in rat enterocyte brush border membranes as an in vitro test sys tem and rats as an in situ absorption model. Derivatives of the cyclic octapeptide octreotide with mono-, di-, and trisaccharide residues we re used. The uptake of octreotide by the vesicles was inhibited by the glycosylated analogs. The uptake was not inhibited by the bicyclic oc tapeptide 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 absorpt ion of the peptides was determined after intrajejunal administration. A linear relationship between inhibitory capacity of the octreotide de rivatives in the vesicle system and their in situ absorption efficienc y was found when blood was taken from a mesenteric vein. However, afte r sampling from a peripheral vein, deviations from the predicted value s 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.