title: Desmopressin duration of antidiuretic action in patients with central diabetes insipidus.
abstract: The key question answered by this study is whether it is possible to deliver a pharmacokinetic and pharmacodynamic duration of antidiuretic action long enough to ensure adequate antidiuresis with two daily administrations of desmopressin in patients with central diabetes insipidus (CDI). We studied the efficacy and safety of desmopressin i.v. in 13 CDI patients using two 3-way crossover designs, in the doses 30, 60, 125 ng, and 125, 250 and 500 ng. Duration of action, minimum output rate, max osmolality and average osmolality during action (AUC osmolality) were measured every 30 min for the first 2 h during the infusion, and then every hour or every second hour until the urine output rate was greater than 2 ml/kg/30 min. The duration of antidiuretic action was 4, 8 and 11 h, respectively, for 125, 250, and 500 ng, increasing from 250 to 500 ng but for the remaining secondary dynamic efficacy parameters no difference could be detected based on descriptive statistics between the doses 250 and 500 ng, indicating that the upper plateau region of the dose-response curve had been reached. All treatment emergent adverse events were classified as unrelated or unlikely related to trial medication. No serious adverse events occurred. Data on duration of action indicates that it is possible to achieve antidiuretic control with 500 ng i.v. corresponding to 160 μg orodispersible tablets twice daily in CDI patients. Today, the Minirin Melt label recommends the majority of CDI patients a dose of 60 to 120 μg t.i.d.
authors.affiliation: Clinical R&D, Medical Science Urology, Ferring Pharmaceuticals A/S, 11 Kay Fiskers Plads, 2300, Copenhagen S, Denmark. kvj@ferring.com
authors.forename: Kristian Vinter
authors.initials: KV
authors.lastname: Juul
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Bichet
authors.forename: Jens Peter
authors.initials: JP
authors.lastname: Nørgaard
mesh_terms: D000284:Administration, Oral; D000328:Adult; D050034:Antidiuretic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D018592:Cross-Over Studies; D003894:Deamino Arginine Vasopressin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D020790:Diabetes Insipidus, Neurogenic / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D012964:Sodium / Q000097:blood; D013894:Thirst / Q000502:physiology; D013997:Time Factors; D016896:Treatment Outcome; D014556:Urine
chemical_list: D050034:Antidiuretic Agents; D012964:Sodium; D003894:Deamino Arginine Vasopressin