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Current Pharmaceutical Design

Editor-in-Chief

ISSN (Print): 1381-6128
ISSN (Online): 1873-4286

Review Article

Developmental Pharmacokinetics in Neonates: Maturational Changes and Beyond

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

Volume 23, Issue 38, 2017

Page: [5769 - 5778] Pages: 10

DOI: 10.2174/1381612823666170926121124

Price: $65

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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