PBPK in Preterm and Term Neonates: A Review

Title:PBPK in Preterm and Term Neonates: A Review

Volume: 23 Issue: 38

Author(s): Robin Michelet*, Jan Van Bocxlaer and An Vermeulen

Affiliation:

• Laboratory of Medical Biochemistry and Clinical Analysis, Department of Bioanalysis, Faculty of Pharmaceutical Sciences, Ghent University,Belgium

Keywords: PBPK, neonates, pharmacokinetics, retrograde approach, bottom-up approach, pediatric drug research.

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.

Cite this article as:

Michelet Robin*, Bocxlaer Van Jan and Vermeulen An, PBPK in Preterm and Term Neonates: A Review, Current Pharmaceutical Design 2017; 23 (38) . https://dx.doi.org/10.2174/1381612823666171009143840

DOI https://dx.doi.org/10.2174/1381612823666171009143840	Print ISSN 1381-6128
Publisher Name Bentham Science Publisher	Online ISSN 1873-4286