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

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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.

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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

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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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Authors and Affiliations

  1. Department of Pediatrics, Faculty of Medicine and Health Sciences, Ghent University, 3K12D, De Pintelaan 185, 9000, Ghent, Belgium

    Pauline De Bruyne

  2. Zeepreventorium, Koninklijke Baan 5, 8420, De Haan, Belgium

    Ann De Guchtenaere

  3. Department of Pediatric Nephrology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Charlotte Van Herzeele, Ann Raes, Jo Dehoorne & Johan Vande Walle

  4. Department of Pediatric Urology, Ghent University Hospital, De Pintelaan 185, 9000, Ghent, Belgium

    Piet Hoebeke & Erik Van Laecke

Authors
  1. Pauline De Bruyne
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  2. Ann De Guchtenaere
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  3. Charlotte Van Herzeele
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  4. Ann Raes
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  5. Jo Dehoorne
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  6. Piet Hoebeke
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  7. Erik Van Laecke
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  8. Johan Vande Walle
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Correspondence to Pauline De Bruyne.

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De Bruyne, P., De Guchtenaere, A., Van Herzeele, C. et al. Pharmacokinetics of desmopressin administered as tablet and oral lyophilisate formulation in children with monosymptomatic nocturnal enuresis. Eur J Pediatr 173, 223–228 (2014). https://doi.org/10.1007/s00431-013-2108-2

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  • DOI: https://doi.org/10.1007/s00431-013-2108-2

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