Central diabetes insipidus in children. Antidiuretic effect and pharmacokinetics of intranasal and peroral 1-deamino-8-D-arginine vasopressin.

The antidiuretic effect and pharmacokinetics of 10 to 20 micrograms of intranasal (IN) and 200 to 400 micrograms of oral (po) 1-deamino-8-D-arginine vasopressin (DDAVP) were studied in 10 paediatric diabetes insipidus patients. A significant increase in urine osmolality was obtained with all doses, maximum within 2 h and still present at 8 h. At 12 h after administration, the ratio urine osmolality/plasma osmolality was above 1 only after 20 micrograms intranasally and 400 micrograms perorally. The free water clearance decreased rapidly with all doses and was similar in magnitude and duration for both the intranasal and peroral routes of administration and remained negative for more than 8 h. The maximum plasma concentrations of DDAVP, measured with a specific and sensitive RIA method, was dose-dependent and there was not significant difference in time until maximum concentration was obtained or in plasma half-life between the two routes of administration. The ratio established, 1:20, by calculating the area under the curve showed a bio-equivalence between 10 micrograms IN and 200 micrograms po and between 20 micrograms IN and 400 micrograms po of DDAVP. This work further emphasized the effectiveness of the oral route and the rapidity of absorption. By continuous monitoring of DDAVP plasma values we have demonstrated that peak values were reached within one hour after administration. This study demonstrates that the doses needed to treat diabetes insipidus patients by the oral route will be approximately 20 times greater than by the nasal route.