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European Journal of Pediatrics

, Volume 173, Issue 2, pp 223–228 | Cite as

Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis

  • Pauline De BruyneEmail author
  • Ann De Guchtenaere
  • Charlotte Van Herzeele
  • Ann Raes
  • Jo Dehoorne
  • Piet Hoebeke
  • Erik Van Laecke
  • Johan Vande Walle
Original Article

Abstract

Desmopressin 120 μg oral lyophilisate and 200 μg tablet are considered bioequivalent, based on extrapolation of studies in a limited number of adults and on one dose-finding study of desmopressin oral lyophilisate in children. However, no comparative pharmacokinetic study in children was executed confirming this statement. No data are available on the influence of food intake on the bioavailability of desmopressin tablet in a pediatric setting, although studies in adults have documented that food intake results in a significantly lower desmopressin plasma concentration. In this study, we analyzed plasma concentrations of desmopressin oral lyophilisate and tablet with concomitant food intake. Twenty-three children with monosymptomatic nocturnal enuresis (mean age, 12.7 years) were recruited. Two tests were performed on two separate days in identical conditions with a standardized food and fluid intake. Desmopressin was administered as desmopressin tablet or desmopressin oral lyophilisate immediately after a meal. Desmopressin plasma concentration was measured at 1 h, 2 h, and 6 h postdosing. No significant difference in plasma concentration of 120 μg desmopressin oral lyophilisate and 200 μg tablet was demonstrated, even with concomitant food intake. A significant difference in variability was found, identifying a smaller variance for desmopressin oral lyophilisate plasma concentrations at all time points. This study demonstrates comparable plasma levels for desmopressin oral lyophilisate, despite the lower dose. The dosage for desmopressin oral lyophilisate is more predictable due to the significantly smaller variance. Therefore, desmopressin oral lyophilisate seems more suitable, especially in the younger age group for which time interval between dinner and drug administration is limited.

Keywords

Pharmacokinetics Desmopressin Monosymptomatic nocturnal enuresis Children 

Abbreviations

dDAVP

1-deamino-8-d-Arginine vasopressin

EMA

European Medicines Agency

ICH

International Conference on Harmonization

LC-MS/MS

Liquid chromatography coupled with tandem mass spectrometry

PIP

Pediatric investigational plan

PK

Pharmacokinetics

PD

Pharmacodynamics

PUMA

Pediatric use marketing authorization

Notes

Acknowledgments

This study was investigator-driven and was in part supported by an unrestricted grant from Ferring International. Pauline De Bruyne has received an independant grant for Strategic Basic Research of the Agency for Innovation by Science and Technology in Flanders (IWT).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Pauline De Bruyne
    • 1
    Email author
  • Ann De Guchtenaere
    • 2
  • Charlotte Van Herzeele
    • 3
  • Ann Raes
    • 3
  • Jo Dehoorne
    • 3
  • Piet Hoebeke
    • 4
  • Erik Van Laecke
    • 4
  • Johan Vande Walle
    • 3
  1. 1.Department of Pediatrics, Faculty of Medicine and Health SciencesGhent UniversityGhentBelgium
  2. 2.ZeepreventoriumDe HaanBelgium
  3. 3.Department of Pediatric NephrologyGhent University HospitalGhentBelgium
  4. 4.Department of Pediatric UrologyGhent University HospitalGhentBelgium

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