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Population pharmacokinetic modeling of a desmopressin oral lyophilisate in growing piglets as a model for the pediatric population

Elke Gasthuys (UGent) , An Vermeulen (UGent) , Siska Croubels (UGent) , Joske Millecam (UGent) , Stijn Schauvliege (UGent) , Thomas van Bergen (UGent) , Pauline De Bruyne (UGent) , Johan Vande Walle (UGent) and Mathias Devreese (UGent)
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Abstract
Desmopressin is used to treat primary nocturnal enuresis in children. Over the years, various formulations of desmopressin were commercialized of which the sublingual melt tablet is preferred in the pediatric population, despite the lack of full PK studies in this population. A full PK study was performed in growing conventional piglets to evaluate if this juvenile animal model can provide supplementary information to complement the information gap in the pediatric population. A desmopressin sublingual melt tablet (120 mu g) was administered to 32 male piglets aged 8 days, 4 weeks, 7 weeks, and 6 months (each group n = 8). Population PK (pop-PK) analysis was performed to derive the PK parameters, the between-and within-subject variabilities and the effects of covariates. Desmopressin demonstrated two-compartmental PK, with a dual, sequential absorption process, and linear elimination. Body weight was the only significant covariate on clearance and on apparent volume of distribution of the central compartment. In human pediatric trials, no double peak in the absorption phase was observed in the plasma concentration-time curves, possibly due to the sparse sampling strategy applied in those pediatric studies. Therefore, it is recommended to perform additional studies, based on the sampling protocol applied in the current study.
Keywords
piglet, animal model, pharmacokinetics, desmopressin, pediatric, NOCTURNAL ENURESIS, CONSCIOUS DOGS, CHILDREN, NATRIURESIS, FORMULATION, VASOPRESSIN, FILTRATION

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Chicago
Gasthuys, Elke, An Vermeulen, Siska Croubels, Joske Millecam, Stijn Schauvliege, Thomas van Bergen, Pauline De Bruyne, Johan Vande Walle, and Mathias Devreese. 2018. “Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population.” Frontiers in Pharmacology 9.
APA
Gasthuys, E., Vermeulen, A., Croubels, S., Millecam, J., Schauvliege, S., van Bergen, T., De Bruyne, P., et al. (2018). Population pharmacokinetic modeling of a desmopressin oral lyophilisate in growing piglets as a model for the pediatric population. FRONTIERS IN PHARMACOLOGY, 9.
Vancouver
1.
Gasthuys E, Vermeulen A, Croubels S, Millecam J, Schauvliege S, van Bergen T, et al. Population pharmacokinetic modeling of a desmopressin oral lyophilisate in growing piglets as a model for the pediatric population. FRONTIERS IN PHARMACOLOGY. 2018;9.
MLA
Gasthuys, Elke, An Vermeulen, Siska Croubels, et al. “Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population.” FRONTIERS IN PHARMACOLOGY 9 (2018): n. pag. Print.
@article{8548575,
  abstract     = {Desmopressin is used to treat primary nocturnal enuresis in children. Over the years, various formulations of desmopressin were commercialized of which the sublingual melt tablet is preferred in the pediatric population, despite the lack of full PK studies in this population. A full PK study was performed in growing conventional piglets to evaluate if this juvenile animal model can provide supplementary information to complement the information gap in the pediatric population. A desmopressin sublingual melt tablet (120 mu g) was administered to 32 male piglets aged 8 days, 4 weeks, 7 weeks, and 6 months (each group n = 8). Population PK (pop-PK) analysis was performed to derive the PK parameters, the between-and within-subject variabilities and the effects of covariates. Desmopressin demonstrated two-compartmental PK, with a dual, sequential absorption process, and linear elimination. Body weight was the only significant covariate on clearance and on apparent volume of distribution of the central compartment. In human pediatric trials, no double peak in the absorption phase was observed in the plasma concentration-time curves, possibly due to the sparse sampling strategy applied in those pediatric studies. Therefore, it is recommended to perform additional studies, based on the sampling protocol applied in the current study.},
  articleno    = {41},
  author       = {Gasthuys, Elke and Vermeulen, An and Croubels, Siska and Millecam, Joske and Schauvliege, Stijn and van Bergen, Thomas and De Bruyne, Pauline and Vande Walle, Johan and Devreese, Mathias},
  issn         = {1663-9812},
  journal      = {FRONTIERS IN PHARMACOLOGY},
  language     = {eng},
  pages        = {9},
  title        = {Population pharmacokinetic modeling of a desmopressin oral lyophilisate in growing piglets as a model for the pediatric population},
  url          = {http://dx.doi.org/10.3389/fphar.2018.00041},
  volume       = {9},
  year         = {2018},
}

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