Abstract: Neonatal drug dosing needs to be based on the physiological characteristics of the newborn and the pharmacokinetic parameters of the drug. Size-related changes can in part be modelled based on allometry and relates to the observation that metabolic rate relates to weight by a kg 0.75 trend. Until adult metabolic activity has been reached, ontogeny, i.e. iso-enzyme specific maturation and maturation of renal clearance also contributes to drug metabolism, making iso-enzyme specific documentation of maturation necessary.
Changes in body composition and ontogeny are most prominent in neonates. The body fat content (/kg) is markedly lower and the body water content (/kg) is markedly higher in neonates. These findings have an impact on the distribution volume of both lipophilic and hydrophilic drugs. Drugs are cleared either by metabolism (metabolic clearance) or elimination (elimination clearance). While the first is mainly hepatic, the second route is mainly renal. Both hepatic metabolism and renal clearance display maturation in early life although other co-variables (e.g. polymorphisms, co-administration of drugs, first pass metabolism, disease characteristics) further contribute to the interindividual variability in drug disposition.
Documentation of these maturational processes based on in vivo ‘case’ studies is of value since these drug-specific observations can subsequently be extrapolated to other drugs which are either already being prescribed or even considered for use in neonates by the introduction of these observations in ‘generic physiologically based pharmacokinetic’ models.

Brief Biography of the Speaker:
Karel Allegaert graduated from the University Leuven, Belgium in 2000 as paediatrician-neonatologist. After an additional training at Sophia Children’s Hospital in Rotterdam, he was appointed as clinical consultant neonatology at the University Hospitals Leuven. After his PhD thesis on neonatal analgesia (2002-2005), he further developed his clinical research in the field of neonatal pain treatment and developmental pharmacology in neonates and was appointed as associated professor at the same university (2005-ongoing). His current clinical research is supported by a grant of the national research council (Fund for Scientific Research, Flanders (Belgium) by a Fundamental Clinical Investigatorship (1800209 N, 2008-2012). This clinical research resulted in about 140 papers published in international peer reviewed journals, conferences proceedings and book chapters and was recently (2009) the Galenus price for research in clinical pharmacology and the Govaerts price for clinical toxicology of the Royal Academy of Medicine of Belgium.