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 > 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.
J. Endocr. (1986) 110, 557–562
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