EFFECTS OF DIFFERENT ABSORPTION ENHANCERS ON THE PERMEATION OF EBIRATIDE, AN ACTH ANALOG, ACROSS INTESTINAL MEMBRANES

The permeation of ebiratide (H-Met(O-2)-Glu-His-Phe-D-Lys-Phe-NH(CH2)( 8)NH2), a novel ACTH analogue, across the intestinal mucosae has been examined by use of isolated intestinal membranes from rats in a modifi ed Ussing chamber. Regional differences were observed in the permeatio n of ebiratide across intestinal membranes; the order of membrane perm eability was jejunum > ileum > duodenum > colon. Overall, the permeati on of ebiratide was relatively poor. The effects of various absorption enhancers were examined to increase the intestinal permeability to eb iratide. Sodium glycocholate and sodium caprate had no significant enh ancing effect on the permeability of the jejunal membrane, but signifi cantly enhanced the permeation of ebiratide through the colonic membra ne. On the other hand, N-dodecyl-beta-D-maltopyramoside (LM) significa ntly enhanced the permeation of ebiratide through both jejunal and col onic membranes. In general, the absorption-enhancing effects of these agents were more predominant in the colon than in the jejunum. Membran e damage by the absorption enhancers was evaluated by measuring the am ount of protein released from the intestinal membrane. It was found th at all the absorption enhancers slightly increased the amount of prote in released, but that the amounts of protein released in the presence of these enhancers were much less than in the presence of ethylenediam inetetraacetic acid (EDTA), used as a positive control. These findings suggest that the absorption enhancers, especially LM might be useful adjuvants for improving the intestinal absorption of peptide and prote in drugs, including ebiratide.