INTESTINAL DELIVERY OF CALCITONIN IN PIG

Salmon calcitonin (sCT) is a 32 amino-acid peptide hormone which has e fficacy in the treatment of osteoporosis and Paget's disease by virtue of a direct inhibitory effect on the bone resorption activity of oste oclasts. In clinical practice the peptide is administered by sub-cutan eous injection, or in some cases intranasally, because the oral availa bility is very low. The formulation employed, known here as Bridgelock , is a solid-dose lipid-based preparation in which the peptide is embe dded directly in the oil phase. We report here results of administerin g this lipidic formulation containing salmon calcitonin, and demonstra te that significant quantities of this hormone pass across the intesti nal wall intact to exert a biological effect in pigs. In a surgically manipulated pig model it has been found that the bio-availability of c alcitonin could be increased when calcitonin is administered in conjun ction with an emulsion-based carrier, giving rise to an order of magni tude increase in pharmacodynamic response as measured by fall in plasm a calcium. At the time of peak fall of calcium, the inter-subject vari ability for the formulation was comparable with that seen for sub-cuta neous administration. In addition, a dose response is demonstrated for the model between 1250 and 5000 iu per pig. Repeatability within the model was confirmed testing the same batch of formulation x months apa rt in a second group of pigs. (C) 1997 Elsevier Science B.V.