89-LB: Oral Administration of Exendin, Using Diabetology’s Axcess Formulation: A Preclinical Study

Exendin-4 was formulated into Diabetology’s Axcess™ formulation, which was administered to adult normal rats, after which both pharmacokinetic and pharmacodynamic parameters were measured. The dry powder formulation was dissolved in water and administered by instillation directly into the intestine of anaesthetized rats. Blood samples were drawn via in-dwelling canulae in the portal and tail veins at various time intervals after administration. Blood levels of exendin-4, measured using standard ELISA methodology, were compared with those after intravenous administration, the relative bioavailabilities calculated being 9% and 18% in the peripheral blood circulation and portal vein respectively. The time course of blood levels is shown in the Figure below. Changes in blood glucose seen after 90 minutes corresponded to levels reported in published literature. A formulation was also administered in which exendin-4 and human insulin were combined, with both peptides being detectable in the portal vein and periphery. Delivery via the intestine accesses the vagal afferents of both the gut and the portal vein, where receptors for GLP-1 agonists are located. The high blood levels of exendin observed, particularly in the portal vein, suggest that this formulation has potential for treatment of diabetes, obesity and metabolic disease after administration of GLP-1 receptor agonists via the oral route.

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