The aim of this study was to characterize the magnitude and duration of the antidiuretic effects elicited by desmopressin given in hemostatic dosage intravenously (i.v.) (0.3 μg/kg) or intranasally (i.n.) (300 μg) both as single or repeated doses (four i.n. doses with 12‐hr intervals) to healthy volunteers. Urine osmolality increased to a maximum median value of 1,087 mOsmol/kg after the single i.v. dose, 1,065 after the single i.n. dose, and 1,071 during the repeated i.n. dosing schedule, and did not differ significantly between the three dosage schedules. The increase lasted for 24 hr after single doses, and 12 hr after the last of the repeated i.n. doses. Serum sodium did not decrease more than normal diurnal variation after single doses, but decreased marginally below the normal reference range in three volunteers after repeated doses. Lowest median serum sodium concentrations after single i.v. and i.n. doses were 140 and 141 mmol/l, respectively, and 139 after repeated i.n. doses. Body weight changed only marginally after single doses, but increased 1.3 kg during repeated dosing. In adult healthy volunteers, single desmopressin doses give an antidiuretic effect lasting for about 24 hr. There is no difference in magnitude or duration between i.v. or i.n. doses. The effect is prolonged as long as the doses are repeated. Serum sodium is only marginally affected by single doses, but tends to decrease after four repeated doses with 12‐hr intervals. If desmopressin is repeated for a period of up to 48 hr, fluid intake should be restricted to 2 liters per day in adults. Am. J. Hematol. 57:153–159, 1998. © 1998 Wiley‐Liss, Inc.

Desmopressin is often used for haemostatic treatment in platelet dysfunction, but the effect kinetics of platelet responses and the mechanism of action are poorly known. This study aimed to determine the kinetics of platelet function responses induced by desmopressin in healthy volunteers treated with aspirin or placebo. Another aim was to correlate platelet responses to changes of von Willebrand factor (vWF) in plasma. We measured platelet function with a glass bead retention test, Ivy bleeding time, vWF:Ag and multimeric structure in plasma. Median baseline platelet retention was 12% (normal reference range 16-27%) during aspirin treatment and 18% during placebo. Median peak platelet retention after desmopressin was 33% during aspirin treatment and 34% during placebo. After about 3 h platelet function had returned to baseline. A second desmopressin dose after 3 h stimulated platelet retention to a similar extent as the first dose. There was no correlation between platelet responses and quantitative or qualitative changes of vWF in plasma. Platelet count did not change significantly. Thus, desmopressin's effect on platelet function lasts for about 3 h, but may be prolonged by a second dose immediately thereafter. These findings may have important clinical implications for patients with aspirin-induced platelet dysfunction undergoing surgery.

The aim of this study was to characterize the magnitude and duration of the antidiuretic effects elicited by desmopressin given in hemostatic dosage intravenously (i.v.) (0.3 µg/kg) or intranasally (i.n.) (300 µg) both as single or repeated doses (four i.n. doses with 12-hr intervals) to healthy volunteers. Urine osmolality increased to a maximum median value of 1,087 mOsmol/kg after the single i.v. dose, 1,065 after the single i.n. dose, and 1,071 during the repeated i.n. dosing schedule, and did not differ significantly between the three dosage schedules. The increase lasted for 24 hr after single doses, and 12 hr after the last of the repeated i.n. doses. Serum sodium did not decrease more than normal diurnal variation after single doses, but decreased marginally below the normal reference range in three volunteers after repeated doses. Lowest median serum sodium concentrations after single i.v. and i.n. doses were 140 and 141 mmol/l, respectively, and 139 after repeated i.n. doses. Body weight changed only marginally after single doses, but increased 1.3 kg during repeated dosing. In adult healthy volunteers, single desmopressin doses give an antidiuretic effect lasting for about 24 hr. There is no difference in magnitude or duration between i.v. or i.n. doses. The effect is prolonged as long as the doses are repeated. Serum sodium is only marginally affected by single doses, but tends to decrease after four repeated doses with 12-hr intervals. If desmopressin is repeated for a period of up to 48 hr, fluid intake should be restricted to 2 liters per day in adults. Am. J. Hematol. 57:153-159, 1998.

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