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PBPK in preterm and term neonates : a review

Robin Michelet (UGent) , Jan Van Bocxlaer (UGent) and An Vermeulen (UGent)
(2017) CURRENT PHARMACEUTICAL DESIGN. 23(38). p.5943-5954
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Abstract
Introduction: The neonatal population remains one of the populations in which appropriate dosing regimens are still lacking, resulting in a large off-label or unlicensed use. Clinical research in these small infants remains a challenge, which sparks the need for modeling and simulation as an additional tool for neonatal drug research. Methods: The use of physiologically based pharmacokinetic modeling in preterm and term neonates is investigated. Results: Throughout the last decade, the use of this modeling technique in this vulnerable population has received increased attention, but still many knowledge gaps exist. Firstly, an overview of the top-down, bottom-up and middle-out approach is given, and then these different modeling tools regarding feasibility and appropriate use are compared. The challenges in applying PBPK to this young population are highlighted and possible solutions are presented. Examples of applications were found in literature and a preference for the combination of a pure bottom-up approach with clinical data (the "middle-out" approach) was detected. Conclusion: Perspectives to further apply this powerful modeling methodology in this population are described in order to become 'the tool' for the design of First-in-Human and First-in-Neonate trials, and the individualization of dosing in these therapeutic orphans.
Keywords
ACCELERATOR MASS-SPECTROMETRY, IN-VITRO DATA, PHYSIOLOGICALLY-BASED, PHARMACOKINETICS, HUMAN UDP-GLUCURONOSYLTRANSFERASES, PLASMA, PARTITION-COEFFICIENTS, PEDIATRIC DRUG DEVELOPMENT, HUMAN, LIVER-MICROSOMES, INTERINDIVIDUAL VARIABILITY, DEVELOPMENTAL, PHARMACODYNAMICS, METABOLIZING-ENZYMES, PBPK, neonates, pharmacokinetics, retrograde approach, bottom-up, approach, pediatric drug research

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Please use this url to cite or link to this publication:

Chicago
Michelet, Robin, Jan Van Bocxlaer, and An Vermeulen. 2017. “PBPK in Preterm and Term Neonates : a Review.” Current Pharmaceutical Design 23 (38): 5943–5954.
APA
Michelet, R., Van Bocxlaer, J., & Vermeulen, A. (2017). PBPK in preterm and term neonates : a review. CURRENT PHARMACEUTICAL DESIGN, 23(38), 5943–5954.
Vancouver
1.
Michelet R, Van Bocxlaer J, Vermeulen A. PBPK in preterm and term neonates : a review. CURRENT PHARMACEUTICAL DESIGN. 2017;23(38):5943–54.
MLA
Michelet, Robin, Jan Van Bocxlaer, and An Vermeulen. “PBPK in Preterm and Term Neonates : a Review.” CURRENT PHARMACEUTICAL DESIGN 23.38 (2017): 5943–5954. Print.
@article{8557047,
  abstract     = {Introduction: The neonatal population remains one of the populations in which appropriate dosing regimens are still lacking, resulting in a large off-label or unlicensed use. Clinical research in these small infants remains a challenge, which sparks the need for modeling and simulation as an additional tool for neonatal drug research. 
Methods: The use of physiologically based pharmacokinetic modeling in preterm and term neonates is investigated. 
Results: Throughout the last decade, the use of this modeling technique in this vulnerable population has received increased attention, but still many knowledge gaps exist. Firstly, an overview of the top-down, bottom-up and middle-out approach is given, and then these different modeling tools regarding feasibility and appropriate use are compared. The challenges in applying PBPK to this young population are highlighted and possible solutions are presented. Examples of applications were found in literature and a preference for the combination of a pure bottom-up approach with clinical data (the {\textacutedbl}middle-out{\textacutedbl} approach) was detected. 
Conclusion: Perspectives to further apply this powerful modeling methodology in this population are described in order to become 'the tool' for the design of First-in-Human and First-in-Neonate trials, and the individualization of dosing in these therapeutic orphans.},
  author       = {Michelet, Robin and Van Bocxlaer, Jan and Vermeulen, An},
  issn         = {1381-6128},
  journal      = {CURRENT PHARMACEUTICAL DESIGN},
  keyword      = {ACCELERATOR MASS-SPECTROMETRY,IN-VITRO DATA,PHYSIOLOGICALLY-BASED,PHARMACOKINETICS,HUMAN UDP-GLUCURONOSYLTRANSFERASES,PLASMA,PARTITION-COEFFICIENTS,PEDIATRIC DRUG DEVELOPMENT,HUMAN,LIVER-MICROSOMES,INTERINDIVIDUAL VARIABILITY,DEVELOPMENTAL,PHARMACODYNAMICS,METABOLIZING-ENZYMES,PBPK,neonates,pharmacokinetics,retrograde approach,bottom-up,approach,pediatric drug research},
  language     = {eng},
  number       = {38},
  pages        = {5943--5954},
  title        = {PBPK in preterm and term neonates : a review},
  url          = {http://dx.doi.org/10.2174/1381612823666171009143840},
  volume       = {23},
  year         = {2017},
}

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