DISTRIBUTION AND KINETICS OF AMYLIN IN HUMANS

The aim of the study was to determine the apparent volume of distribut ion (V-TOT), total body clearance (CL), fractional clearance, and mean residence time (MRT) of the beta-cell hormone amylin. We therefore pe rformed an intravenous injection of 50 mu g of human synthetic amylin (amlintide) in nine healthy male subjects during suppression of endoge nous amylin release by intravenous somatostatin (0.06 mu g.kg2(-1). mi n(-1)). The plasma levels of amylin concentrations over time were anal yzed using three-exponential curves. V-TOT was 173 +/- 16 ml/kg and wa s not different from that of insulin reported in the literature (157 m l/kg). MRT was 27.7 +/- 2.1 min and thus two times the reported value for insulin (14.1 min) and C-peptide (16.4 min). CL and fractional CL were 6.2 +/- 0.2 ml.kg(-1).min(-1) and 0.038 +/- 0.003 min(-1), respec tively. Fractional CL is therefore definitely lower than that reported for insulin (0.12-0.2 min(-1)) but is, however, in the range of that of C-peptide (0.05 min(-1)). In conclusion, clearance of amylin is sim ilar to that reported for C-peptide and much slower than insulin, indi cating that the commonly used molar insulin-to-amylin ratio does not r eflect the correct relationship of the two peptides.