Abstract
Tetragastrin (TG) has a potent pharmacological activity as gastrin. However, the oral bioavailability of TG is extremely low(about 3%) because of its high hydrophilicity and extensive hydrolysis in the gastrointestinal mucosa. in order to improve intestinal absorption of TG, we synthesized a new lipophilic derivative of TG by chemical modification of the peptide with caproic acid, and caproyl-TG (Cap-TG) was obtained. Cap-TG was confirmed to be more lipophilic than TG by high performance liquid chromatography. Intravenous injection of Cap-TG showed 1.7 fold higher activity than TG. The gastric acid secretion activities of these compounds were measured in rats after intestinal administration. When Cap-TG was administered into large intestinal loop, a marked increase in gastric acid secretion was observed in comparison with TG, while we found no significant effect following the small intestinal administration of Cap-TG. These results indicated that chemical modification of TG with caproic acid might be a useful approach for improving the large intestinal absorption of TG.
