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.
Current Pharmaceutical Design
Title:Developmental Pharmacokinetics in Neonates: Maturational Changes and Beyond
Volume: 23 Issue: 38
Author(s): Karel Allegaert*, Paola Mian and John N. van den Anker
Affiliation:
- Intensive Care and Department of Pediatric Surgery, Erasmus MC Sophia Children's Hospital, Rotterdam,Netherlands
Keywords: Pharmacokinetics, newborn, absorption, distritubion, metabolism, elimination, neonatal clinical pharmacology.
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.Export Options
About this article
Cite this article as:
Allegaert Karel*, Mian Paola and van den Anker N. John, Developmental Pharmacokinetics in Neonates: Maturational Changes and Beyond, Current Pharmaceutical Design 2017; 23 (38) . https://dx.doi.org/10.2174/1381612823666170926121124
DOI https://dx.doi.org/10.2174/1381612823666170926121124 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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