The antidiuretic action of 1-deamino-8-D-arginine vasopressin (DDAVP) in man

1. After administration of a new vasopressin analogue (DDAVP), a marked and prolonged antidiuresis occurred in 10 patients with pituitary diabetes insipidus. 2. The antidiuretic effects of single intravenous doses of 0.04--24 mug DDAVP and single intranasal doses of 5--320 mug DDAVP were investigated. Time curves of the antidiuretic responses expressed in changes of urine osmolality (Uosm) and free water clearance per 100 ml GFR (CH2O X 100/GFR) are described. 3. Maximal "peak" response was obtained after an intravenous dose of 1 mug within the first 12 hrs (Uosm was 7--800 mOsm/KgH2O). Further increase of dosage resulted only in prolongation of duration of action (up to 48 hrs) and peak ("plateau") effect (up to 24 hrs). 4. There was a linear relationship between the log dose and log osmolality of urine collected in the second 12 hours after administration of single intravenous and intranasal doses of DDAVP. 5. Comparison of the effects of 1 mug lysine-vasopressin and 1 mug DDAVP revealed only slight differences in peak effects, but extreme differences in duration of action. 6. It is concluded that in the evaluation of a synthetic vasopressin analogue the maximal antidiuretic ability and the prolongation of action have to be analysed separately.