title: Pharmacokinetics and renal excretion of desmopressin after intravenous administration to healthy subjects and renally impaired patients.
abstract: OBJECTIVE
  To evaluate the influence of renal impairment on the pharmacokinetics of desmopressin.
  
  
  METHODS
  Twenty-four subjects were enrolled in the study, 18 with varying degrees of renal impairment and six healthy volunteers. Each subject received a single intravenous dose of 2 microg desmopressin. Blood and urine samples were collected for 24 h and assayed for desmopressin by radioimmunoassay. Plasma concentrations and the amounts of desmopressin excreted in the urine were analysed simultaneously by use of mixed effects modelling.
  
  
  RESULTS
  Only mild adverse events were observed. Both the renal and the nonrenal clearance of desmopressin were found to vary with the creatinine clearance (CrCL). A decrease of 1.67% in the CrCL (corresponding to 1 ml min(-1) from 60 ml min(-1)) was found to cause a 1.74% decrease in the renal clearance and a 0.93% decrease in the nonrenal clearance. The fall in renal clearance caused the amount of desmopressin excreted in urine to decrease from 47% in healthy subjects to 21% in the patients with severe renal impairment. The mean systemic clearance of desmopressin was 10 litres h(-1) in healthy subjects and 2.9 litres h(-1) in patients with severe renal impairment (difference -7.5 litres h(-1), 95% CI [-11; -4.3] litres h(-1)). Correspondingly, the mean terminal half-life, was 3.7 h in healthy subjects and 10 h in patients with severe renal impairment (difference 6.7 h, 95% CI [4.0; 9.4] h).
  
  
  CONCLUSIONS
  Although desmopressin appears to be safe and well-tolerated by patients with impaired renal function, great caution should be exercised when titrating towards an efficient dosage regimen if patients with moderately or severely impaired renal function are to be treated with desmopressin at all.
authors.affiliation: Experimental Medicine, Ferring Pharmaceuticals A/S, Denmark. henrik.agersoe@ferring.com
authors.forename: Henrik
authors.initials: H
authors.lastname: Agersø
authors.forename: Lotte
authors.initials: L
authors.lastname: Seiding Larsen
authors.forename: Anders
authors.initials: A
authors.lastname: Riis
authors.forename: Ulf
authors.initials: U
authors.lastname: Lövgren
authors.forename: Mats O
authors.initials: MO
authors.lastname: Karlsson
authors.forename: Thomas
authors.initials: T
authors.lastname: Senderovitz
mesh_terms: D000368:Aged; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000378:metabolism*; D008875:Middle Aged; D011446:Prospective Studies; D012076:Renal Agents / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*
chemical_list: D012076:Renal Agents; D003894:Deamino Arginine Vasopressin