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Desmopressin duration of antidiuretic action in patients with central diabetes insipidus

Juul, Kristian Vinter; Bichet, Daniel G. and Norgaard, Jens Peter LU (2011) In Endocrine 40(1). p.67-74
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... (More)
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 mu g orodispersible tablets twice daily in CDI patients. Today, the Minirin Melt label recommends the majority of CDI patients a dose of 60 to 120 mu g t.i.d. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Desmopressin, Central diabetes insipidus, Antidiuresis, Duration of, action
in
Endocrine
volume
40
issue
1
pages
67 - 74
publisher
Humana Press
external identifiers
  • wos:000293408900010
  • scopus:80755153660
ISSN
1355-008X
DOI
10.1007/s12020-011-9492-z
language
English
LU publication?
yes
id
7a411ee2-166a-4c5d-b579-db5607d6b860 (old id 2162082)
date added to LUP
2011-10-03 08:37:48
date last changed
2017-02-22 11:44:17
@article{7a411ee2-166a-4c5d-b579-db5607d6b860,
  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 mu g orodispersible tablets twice daily in CDI patients. Today, the Minirin Melt label recommends the majority of CDI patients a dose of 60 to 120 mu g t.i.d.},
  author       = {Juul, Kristian Vinter and Bichet, Daniel G. and Norgaard, Jens Peter},
  issn         = {1355-008X},
  keyword      = {Desmopressin,Central diabetes insipidus,Antidiuresis,Duration of,action},
  language     = {eng},
  number       = {1},
  pages        = {67--74},
  publisher    = {Humana Press},
  series       = {Endocrine},
  title        = {Desmopressin duration of antidiuretic action in patients with central diabetes insipidus},
  url          = {http://dx.doi.org/10.1007/s12020-011-9492-z},
  volume       = {40},
  year         = {2011},
}