Prolonged antidiuresis by 1-desamino-8-D-arginine vasopressin (DDAVP): Correlation to its plasma levels and nephrogenous cyclic AMP production.

Abstract

To clarify the mechanism responsible for the prolonged effect of DDAVP (1-desamino-8-D-arginine vasopressin), plasma levels of DDAVP and nephrogenous cAMP were determined in patients with diabetes insipidus after a single intranasal administration of 10 .mu.g DDAVP. Plasma DDAVP levels were uniformly elevated within 30 min, and showed a peak ranging from 5.6-25.0 pg/ml between 30 and 120 min. The subsequent time-course of plasma DDAVP differed from patient to patient, and was irregular in most of them. In all patients whose plasma DDAVP dropped below 1.0 pg/ml, antidiuresis was still observed. Although the mean basal level of nephrogenous cAMP in patients with diabetes insipidus was not significantly different from that in control subjects. the administration of DDAVP resulted in a 2-fold increase. A negative correlation between nephrogenous cAMP and free H2O clearance was obtained. The long-acting nature of DDAVP may be due to its gradual absorption from nasal mucosa and slow metabolic clearance and to a higher or persistent biological activity at the receptor site in the kidney. A nearly physiological level of antidiuretic hormone may cause de novo synthesis of cAMP in the kidney and exert its biological action.