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Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population
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 per...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797931/ https://www.ncbi.nlm.nih.gov/pubmed/29445339 http://dx.doi.org/10.3389/fphar.2018.00041 |
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author | Gasthuys, Elke Vermeulen, An Croubels, Siska Millecam, Joske Schauvliege, Stijn van Bergen, Thomas De Bruyne, Pauline Vande Walle, Johan Devreese, Mathias |
author_facet | Gasthuys, Elke Vermeulen, An Croubels, Siska Millecam, Joske Schauvliege, Stijn van Bergen, Thomas De Bruyne, Pauline Vande Walle, Johan Devreese, Mathias |
author_sort | Gasthuys, Elke |
collection | PubMed |
description | 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 μg) 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. |
format | Online Article Text |
id | pubmed-5797931 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-57979312018-02-14 Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population Gasthuys, Elke Vermeulen, An Croubels, Siska Millecam, Joske Schauvliege, Stijn van Bergen, Thomas De Bruyne, Pauline Vande Walle, Johan Devreese, Mathias Front Pharmacol Pharmacology 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 μg) 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. Frontiers Media S.A. 2018-01-31 /pmc/articles/PMC5797931/ /pubmed/29445339 http://dx.doi.org/10.3389/fphar.2018.00041 Text en Copyright © 2018 Gasthuys, Vermeulen, Croubels, Millecam, Schauvliege, van Bergen, De Bruyne, Vande Walle and Devreese. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Pharmacology Gasthuys, Elke Vermeulen, An Croubels, Siska Millecam, Joske Schauvliege, Stijn van Bergen, Thomas De Bruyne, Pauline Vande Walle, Johan Devreese, Mathias Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population |
title | Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population |
title_full | Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population |
title_fullStr | Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population |
title_full_unstemmed | Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population |
title_short | Population Pharmacokinetic Modeling of a Desmopressin Oral Lyophilisate in Growing Piglets as a Model for the Pediatric Population |
title_sort | population pharmacokinetic modeling of a desmopressin oral lyophilisate in growing piglets as a model for the pediatric population |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797931/ https://www.ncbi.nlm.nih.gov/pubmed/29445339 http://dx.doi.org/10.3389/fphar.2018.00041 |
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