DDAVP (l-Desamino-8-D-arginine-vasopressin) Treatment of Central Diabetes Insipidus—Mechanism of Prolonged Antidiuresis*

Abstract

DDAVP is a synthetic analog of arginine vasopressin which produces prolonged antidiuresis after intranasal administration to patients with complete central diabetes insipidus. The mechanism of the prolonged antidiuretic effect was studied by specific radioimmunoassay of DDAVP in plasma of patients and by in vitro studies on the adenylate cyclase-cyclic[c]AMP system of the rat outer renal medulla. When DDAVP was administered to patients, all responded, but the duration of response among patients varied from 5-21 h. The peak level of DDAVP in plasma was achieved up to 4 h after administration indicating a slow absorption from the nasal mucosa. The disappearance time of DDAVP from plasma correlated significantly with the duration of antidiuresis, P < 0.001. On a molar basis DDAVP was 3-fold greater than AVP in its stimulation of outer medullary adenylate cyclase activity and 10-fold greater than AVP in its stimulation of cAMP content. The prolonged antidiuresis of intranasally administered DDAVP is due to slow absorption, persistence in plasma and enhanced effect on the kidney.