Developmental Pharmacokinetics in Neonates: Maturational Changes and Beyond

Author(s): Karel Allegaert*, Paola Mian, John N. van den Anker

Journal Name: Current Pharmaceutical Design

Volume 23 , Issue 38 , 2017


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Abstract:

Background: Effective and safe pharmacotherapy in an individual neonate necessitates understanding the pharmacokinetic (PK) and pharmacodynamic (PD) properties of a specific drug together with the characteristics of this neonate.

Methods: Developmental PK hereby provides estimates of the concentration-time profile. Multiple maturational, disease and treatment related differences can result in differences in PK and probably also in PD in neonates compared to other populations. All these PK processes (absorption, distribution, metabolism and elimination, ADME) display maturation but are also affected by non-maturational covariates. Maturational covariates relate to age or weight dependent changes, while non-maturational covariates relate to variables in disease, environment, treatment – including co-medications - or genetic background.

Results: We will describe general PK related aspects of ADME in neonates with emphasis on both maturational and non-maturational covariates of the variability observed, followed by compound specific illustrations (tramadol, amikacin) to further underscore the impact and interaction of these maturational and non-maturational changes.

Conclusion: Future efforts should focus on integration of the already available knowledge and the collection of data on the impact of non-maturational covariates. These kinds of PK efforts will become clinically important when subsequently linked to PD, ultimately covering both wanted effects and undesired side-effects.

Keywords: Pharmacokinetics, newborn, absorption, distritubion, metabolism, elimination, neonatal clinical pharmacology.

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Article Details

VOLUME: 23
ISSUE: 38
Year: 2017
Published on: 09 February, 2018
Page: [5769 - 5778]
Pages: 10
DOI: 10.2174/1381612823666170926121124
Price: $65

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