THE COLONIC ABSORPTION OF HUMAN CALCITONIN - THE EFFECTS OF INCREASING LOCAL CONCENTRATION AND COADMINISTRATION WITH A PROTEASE INHIBITOR

Attention has recently focused on the colon as a potential site to tar get therapeutic peptides and proteins for systemic absorption. This pa per describes the colonic absorption of human calcitonin (hCT) in man. Low concentrations of human hCT are rapidly degraded by human faecal material. This degradation can be retarded by addition of the protease inhibitor aprotinin. The absolute bioavailability (ABV) of 10 mg hCT administered in a high concentration to the descending colon of nine h ealthy volunteers was 0.22 +/- 0.07%. The maximum plasma concentration was 1208 +/- 357 pg ml(-1), observed after 5 min. The co-administrati on of aprotinin with 10 mg hCT decreased the ABV to 0.11 +/- 0.03%, an d the plasma profile gave a maximum concentration of 442 +/- 115 pg ml (-1), observed after 10 min. High local concentrations of hCT in the c olon improve absorption, but do not alter the plasma profile of the pe ptide.