ORAL-ADMINISTRATION OF PEPTIDES - STUDY OF A GLYCEROLIPIDIC PRODRUG

In order to explore the possibility of administering a peptide by the oral route, a diglyceride prodrug of a pentapeptide has been evaluated in vitro and in vivo. Different formulations of the prodrug have been studied: an aqueous suspension, different o/w emulsions, an oily solu tion and different aqueous solutions in which the prodrug was solubili zed with the aid of taurocholate in the presence of palmitic acid or c alcium chloride. The stability of the prodrug in a lipase medium was c orrelated with its solubility in the aqueous phase. The lymphatic kine tics after oral administration of the peptide prodrug have been determ ined after mesenteric lymphatic cannulation in the rat. The lymphatic uptake of the prodrug has been found to be somewhat erratic and finall y, the prodrug does not seem to cross intact the enteral barrier. Diff erent hypotheses are proposed to explain these results.