Pharmaceutical research and metabolomics in the newborn.

Newborns are a particularly vulnerable population. The response to a drug in terms of efficacy and toxicity varies widely from one newborn to another. Inter-individual variation in drug response is strongly affected by the patient's biochemical state at the time of therapy, as reflected by his metabolic phenotype, which in turn results from the interaction of both genetic and non-genetic factors. These factors contribute to the difficulties in accurate drug prescribing and dosing and to the increased risk of adverse drug reactions in the neonatal population. Metabolomics has been found to be particularly suitable for pharmaceutical Research & Development, with a range of successful applications that include preclinical safety evaluation of drug candidates, predicting the metabolism and toxicity of a drug based on the analysis of a pre-dose metabolic profile (pharmacometabolomics), and identification of drug-related alterations in metabolic pathways. Pharmacometabolomics is a rapidly developing field which refers to the direct measurement of metabolites in an individual's body fluids to predict or evaluate the metabolism of pharmaceuticals. The implementation of metabolomic techniques in pharmaceutical research has the potential to greatly enhance our understanding of mechanisms of drug effects, of undesirable drug reactions and of the biological processes underlying individual variations in drug response phenotypes. A more extensive clinical use of metabolomics could be a decisive step towards personalized drug therapy, with the ultimate aim to match the right drug to the right patient. Some applications of metabolomics in pharmaceutical research are discussed, with special focus on clinical use in Neonatology.