ENHANCEMENT OF HUMAN CALCITONIN ABSORPTION ACROSS THE RAT COLON IN-VIVO

We have studied the influence of equimolar monoolein: sodium taurocholate enhancer formulations on the absorption of human calcitonin (hCT) and two markers of intestinal permeability, horseradish peroxidase (HRP) and polyethylene glycol, molecular weight 4000 (PEG 4000). hCT, HRP and PEG 4000 were air absorbed across the colonic mucosa to a limited extent. The use of 40 mM monoolein:40 mM sodium taurocholate significantly (p < 0.001) enhanced (9.0 +/- 1.0-fold) the absorption of all three molecules with no damage to the mucosal tissue at the light microscopy level At concentrations of 20 mM and below, the monoolein:sodium taurocholate formulation did not enhance the absorption of hCT. HRP immunohistochemistry showed an intracellular localisation suggesting that the transcellular pathway was involved in the absorption process; The increased absorption of hCT in the presence of the 40 mM enhancer formulation was able to elicit a maximal hypocalcaemic response, whereas no significant effect was observed in the absence of the enhancer. We conclude that the absorption enhancer used in this study, can increase intestinal absorption of a range of molecules without causing major tissue damage. Such formulations may offer advantages as they enable pharmacodynamic responses to be elicited from smaller doses of therapeutic peptides and proteins.