Pharmacokinetics and antidiuretic effect of intravenous administration of desmopressin in orally overhydrated male volunteers.

In order to study the antidiuretic activity of desmopressin in healthy human subjects, a study design has previously been used with subjects orally hydrated. The objective of the present study was to investigate the pharmacokinetics and the antidiuretic activity of desmopressin administered as an intravenous infusion to eight orally hydrated male volunteers. After initial ingestion of water corresponding to 15 ml.kg-1 body weight, the overhydration was maintained by replacing the urinary fluid loss by drinking-water. Desmopressin (4 micrograms) was administered intravenously over 10 min. 1.5 hr after the start of the hydration procedure. Blood was sampled and urine was collected at intervals throughout the study day (9.5 hr). The terminal half-life of elimination (t1/2,) of desmopressin was calculated to be 2.97 +/- 0.24 (S.E.M.) hr while the clearance was 1.77 +/- 0.10 ml.min.-1.kg-1 and the volume of distribution at steady state was 373 +/- 30 ml.kg-1. The infusion caused a marked and long-lasting reduction of the urine flow rate. Four hr after the start of the infusion the mean urine osmolality was 909 +/- 46 mOsm.kg-1.