Developmental pharmacokinetics in neonates

Abstract

Safe and effective administration of drugs in neonates requires an understanding of the developmental aspects of drug disposition. In neonates, interindividual variability in disposition of drugs is extensive. Renal elimination clearance of drugs is decreased owing to immaturity of renal function, while metabolic clearance displays iso-enzyme-specific ontogeny, that is, depends mainly on postmenstrual and/or postnatal age. Besides age (maturation), the route of administration, codiseases, coadministration of drugs, and polymorphisms in drug-metabolizing enzymes or transporters also emerge as contributors of this interindividual variability. Throughout this review, we provide the reader with references to the available clinical research tools to document these maturational changes in neonates. The major challenge will be to integrate the available knowledge into both clinical care and clinical pharmacology research to further ensure safe and effective prescription. The legal initiatives, including Paediatric Drug Regulation in the EU, and effective research tools, including population pharmacokinetics, are two important stimulants to boost further progress in this field.