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Pharmacokinetics and antidiuretic effect of high-dose desmopressin in patients with chronic renal failure.

High-dose desmopressin shortens the bleeding time in uraemia. The aim of this study was to investigate the pharmacokinetics and the antidiuretic effect of desmopressin when given in a dose normally used for haemostasis to patients with reduced renal function. Ten patients with chronic renal failure of varying aetiology were enrolled in the study. The age was 58 (20-76) years (median and range), serum creatinine 447 (309-691) micromol/l and plasma clearance of iohexol 16 (8-19) ml/min./1.73 m2 body surface. After baseline measurements, desmopressin was infused at a dose of 0.3 microg/kg. The plasma concentration of desmopressin was followed for 26 hr during and after the infusion and the pharmacokinetic parameters were estimated by compartmental analysis. Urine volume and osmolality, as well as body weight, blood pressure, heart rate, haematocrit, serum osmolality, electrolytes and creatinine, were measured repeatedly during the day before and for two days after the infusion. The total clearance of desmopressin was 0.35 (0.21-0.47) ml/min./kg, the volume of distribution at steady state was 0.30 (0.17-0.38) l/kg and the terminal half-life 9.7 (8.4-16) hr. After administration of desmopressin, urine osmolality increased significantly, by approximately 10%, and this increase lasted for 48 hr. Concomitantly, there was a modest but significant decrease in haematocrit. Thus, the clearance of desmopressin was on average decreased to approximately one quarter, and the terminal half-life was prolonged 2-3 times in the patients as compared to previously published values for healthy adults. The single haemostatic dose of desmopressin given to patients with severe renal failure did not cause fluid overload or changes in serum electrolytes.