[3H]9-desglycinamide,8-arginine vasopressin: metabolism and in-vivo fate.
Half-lives based on the disappearance of [3H]9-desglycinamide,8-arginine vasopressin ([3H]DGAVP) following in-vitro incubation in plasma were 1.7 h (dog), 5.8 h (rat) and greater than 12 h (man). For all three species, and particularly dogs, biotransformation of the peptide in plasma occurred predominantly through carboxypeptidase activities, leading to the accumulation of AVP-(1-7). Disappearance of [3H]DGAVP from rat blood after a single i.v. injection followed a biphasic decay with half-lives of 2.2 +/- 0.8 (S.D.) min (distribution phase) and 14.4 +/- 1.2 min (elimination phase). The central and peripheral volumes of distribution were high and of the same order of magnitude, being 0.21 and 0.25 litres/kg respectively. Blood clearance values ranged from 36 to 45 ml/min per kg. In addition to [3H]AVP-(1-7), [3H]tyrosine was also found to be a major radioactive metabolite in blood. Compared with i.v. dosing, the s.c. route of administration for [3H]DGAVP resulted in longer-lasting peptide levels in blood which persisted for up to 4-5 h after injection. Maximal concentrations were reached at 7.5 min, whereafter they declined bi-exponentially with terminal half-lives of 31.1 +/- 8.7 min. The mean bioavailability for DGAVP was almost 100%, demonstrating virtually complete absorption from the s.c. injection site.
D000818:Animals; D001127:Arginine Vasopressin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood / Q000378:metabolism; D001682:Biological Availability; D004285:Dogs; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008657:Metabolic Clearance Rate; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014443:Tyrosine / Q000378:metabolism
D010446:Peptide Fragments; D001127:Arginine Vasopressin; C015119:argipressin, des-GlyNH2(9)-; C049092:argipressin (1-7); D014443:Tyrosine