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
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.