Clinical pharmacology in neonates: small size, huge variability.

Drug therapy is a powerful tool for improving neonatal outcome. Despite this, neonatologists still routinely prescribe off-label compounds developed for adults and extrapolate doses from those used for children or adults. Knowledge integration through pharmacokinetic modeling is a method that could improve the current situation. Such predictive models may convert neonatal pharmacotherapy from explorative to confirmatory. This can be illustrated by research projects related to the prediction of neonatal renal clearance and neonatal glucuronidation. This type of model will also improve the current knowledge of neonatal (patho)physiology. In the meanwhile, the fields of clinical pharmacology (e.g. pharmacokinetic/pharmacodynamic modeling and pharmacogenetics) and neonatology (e.g. whole-body cooling and the lower limit of viability) have both matured, resulting in new research topics. However, in order for the modeling and the newly emerging topics to become effective tools, they need to be tailored to the specific characteristics of neonates. Consequently, the field of neonatal pharmacotherapy needs dedicated neonatologists who continue to raise the awareness that off-label practices, eminence-based dosing regimens and the absence of neonatal drug formulations all reflect suboptimal care.