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Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray

Ann De Guchtenaere UGent, Ann Raes UGent, CAROLINE VANDE WALLE UGent, Piet Hoebeke UGent, Erik Van Laecke UGent, Raymond AMG Donckerwolcke and Johan Vande Walle UGent (2009) JOURNAL OF UROLOGY. 181(1). p.302-309
abstract
Purpose: Desmopressin is an evidence-based medicine level 1, category A therapy for monosymptomatic nocturnal enuresis. However, in up to 40% of patients only partial desmopressin response is obtained. While the poor pharmacokinetic characteristics of the different available formulations may have a role in apparent therapy resistance, there are limited data available to support this theory. We sought to identify pharmacodynamic factors involved in partial desmopressin response or desmopressin resistance in children with monosymptomatic nocturnal enuresis, with special emphasis on concentrating performance, and time to reach and duration of maximal urine concentration. Materials and Methods: We evaluated 64 children with monosymptomatic nocturnal enuresis and proved nocturnal polyuria lacking full response to desmopressin treatment. The study involved 2 separate home based test days (A and B), each consisting of 9 timed urine collections starting in the evening 1 hour before desmopressin administration and continuing for 16 hours following desmopressin administration. Test A was done during fluid restriction, and test B was done during an oral fluid load. Results: Under fluid restriction 16 patients failed to achieve urine concentration greater than 850 mOsmol/l at the midnight collection following desmopressin administration. After an oral fluid load given at the start of the test the majority of patients failed to reach maximal concentration of urine as voided during hydropenia, and 45 patients failed to regain appropriate dilution of urine even when an oral water load of 15 ml/kg (urine osmolality less than 750 mOsmol/l) was given in the morning at the end of the test. This finding is suggestive of a prolonged duration of action of the drug. Conclusions: Pharmacodynamic tests reveal a suboptimal effect of desmopressin on urine concentration in a significant percentage of patients, which worsens when fluid is not restricted before desmopressin administration. Also the time to reach maximal antidiuretic effect and the duration of pharmacodynamic action show a wide range, requiring individualization of mode and time of administration. Our data demonstrate that a simple pharmacodynamic test as described may give important information on time of dosing, duration of action and influence of oral fluid intake, allowing individualization of therapy. Data also reveal that desmopressin should be administered at least 1 hour before bedtime, and that in case of therapy resistance a longer interval, up to 2 hours, might further reduce diuresis rate in the early night. Because of the documented prolonged action of desmopressin in some patients, increasing the dose without performing pharmacodynamic testing is no longer acceptable.
Please use this url to cite or link to this publication:
author
organization
year
type
journalArticle (original)
publication status
published
journal title
JOURNAL OF UROLOGY
J. Urol.
volume
181
issue
1
pages
302 - 309
publisher
ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH
place of publication
NEW YORK, NY 10010-1710 USA
Web of Science type
Article
Web of Science id
000261705900171
JCR category
UROLOGY & NEPHROLOGY
JCR impact factor
4.016 (2009)
JCR rank
8/61 (2009)
JCR quartile
1 (2009)
ISSN
0022-5347
DOI
10.1016/j.juro.2008.09.040
language
English
UGent publication?
yes
classification
A1
id
526285
handle
http://hdl.handle.net/1854/LU-526285
date created
2009-03-19 14:41:22
date last changed
2015-06-17 11:08:57
@article{526285,
  abstract     = {Purpose: Desmopressin is an evidence-based medicine level 1, category A therapy for monosymptomatic nocturnal enuresis. However, in up to 40\% of patients only partial desmopressin response is obtained. While the poor pharmacokinetic characteristics of the different available formulations may have a role in apparent therapy resistance, there are limited data available to support this theory. We sought to identify pharmacodynamic factors involved in partial desmopressin response or desmopressin resistance in children with monosymptomatic nocturnal enuresis, with special emphasis on concentrating performance, and time to reach and duration of maximal urine concentration.
Materials and Methods: We evaluated 64 children with monosymptomatic nocturnal enuresis and proved nocturnal polyuria lacking full response to desmopressin treatment. The study involved 2 separate home based test days (A and B), each consisting of 9 timed urine collections starting in the evening 1 hour before desmopressin administration and continuing for 16 hours following desmopressin administration. Test A was done during fluid restriction, and test B was done during an oral fluid load.

Results: Under fluid restriction 16 patients failed to achieve urine concentration greater than 850 mOsmol/l at the midnight collection following desmopressin administration. After an oral fluid load given at the start of the test the majority of patients failed to reach maximal concentration of urine as voided during hydropenia, and 45 patients failed to regain appropriate dilution of urine even when an oral water load of 15 ml/kg (urine osmolality less than 750 mOsmol/l) was given in the morning at the end of the test. This finding is suggestive of a prolonged duration of action of the drug.

Conclusions: Pharmacodynamic tests reveal a suboptimal effect of desmopressin on urine concentration in a significant percentage of patients, which worsens when fluid is not restricted before desmopressin administration. Also the time to reach maximal antidiuretic effect and the duration of pharmacodynamic action show a wide range, requiring individualization of mode and time of administration. Our data demonstrate that a simple pharmacodynamic test as described may give important information on time of dosing, duration of action and influence of oral fluid intake, allowing individualization of therapy. Data also reveal that desmopressin should be administered at least 1 hour before bedtime, and that in case of therapy resistance a longer interval, up to 2 hours, might further reduce diuresis rate in the early night. Because of the documented prolonged action of desmopressin in some patients, increasing the dose without performing pharmacodynamic testing is no longer acceptable.},
  author       = {De Guchtenaere, Ann and Raes, Ann and VANDE WALLE, CAROLINE and Hoebeke, Piet and Van Laecke, Erik and Donckerwolcke, Raymond AMG and Vande Walle, Johan},
  issn         = {0022-5347},
  journal      = {JOURNAL OF UROLOGY},
  language     = {eng},
  number       = {1},
  pages        = {302--309},
  publisher    = {ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH},
  title        = {Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray},
  url          = {http://dx.doi.org/10.1016/j.juro.2008.09.040},
  volume       = {181},
  year         = {2009},
}

Chicago
De Guchtenaere, Ann, Ann Raes, CAROLINE VANDE WALLE, Piet Hoebeke, Erik Van Laecke, Raymond AMG Donckerwolcke, and Johan Vande Walle. 2009. “Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray.” Journal of Urology 181 (1): 302–309.
APA
De Guchtenaere, A., Raes, A., VANDE WALLE, C., Hoebeke, P., Van Laecke, E., Donckerwolcke, R. A., & Vande Walle, J. (2009). Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray. JOURNAL OF UROLOGY, 181(1), 302–309.
Vancouver
1.
De Guchtenaere A, Raes A, VANDE WALLE C, Hoebeke P, Van Laecke E, Donckerwolcke RA, et al. Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray. JOURNAL OF UROLOGY. NEW YORK, NY 10010-1710 USA: ELSEVIER SCIENCE INC, 360 PARK AVE SOUTH; 2009;181(1):302–9.
MLA
De Guchtenaere, Ann, Ann Raes, CAROLINE VANDE WALLE, et al. “Evidence of Partial Anti-Enuretic Response Related to Poor Pharmacodynamic Effects of Desmopressin Nasal Spray.” JOURNAL OF UROLOGY 181.1 (2009): 302–309. Print.