Developmental Pharmacology and Therapeutics in Neonatal Medicine
Knowledge about the safe and effective use of medicines in neonates has increased substantially but resulted in few label changes. Despite the extent of these drug exposures, newborns remain the last therapeutic orphans. Drugs, initially developed for use in adults, are reshaped and tailored to specific neonatal indications. However, neonatal pharmacotherapy not only mirrors adult pharmacotherapy but should be driven by their own specific needs. This is because both pharmacokinetics (absorption, distribution, metabolism, elimination, concentration-time) and pharmacodynamics (concentration-effect) display extensive maturation in early infancy, reflecting maturational physiology. We describe and illustrate the relevance of these maturational changes. We subsequently focus on specific aspects related to therapeutic drug monitoring, the need for population tailored neonatal formulations (including dose flexibility and excipients), and the difficulties related to the recognition of adverse drug reactions in neonates (how to recognize a signal in the noise).
Karel Allegaert is supported by the Fund for Scientific Research, Flanders (fundamental clinical investigatorship 1800214 N), and the research activities are further facilitated by the agency for innovation by Science and Technology in Flanders (IWT) through the SAFEPEDRUG project (IWT/SBO 130033). Janko Samardzic is supported by ERAWEB II scholarship for postdoctoral program at the KU Leuven, Belgium (2014–2015). Milica Bajcetic is supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (project No 173014) and the European Commission (LENA, 602295). John van den Anker is supported by NIH (K24DA027992, R01HD048689, U54HD071601) and the European Commission (TINN , TINN2 , NEUROSIS ).
- Carvalho CG, Ribeiro MR, Bonilha MM et al (2012) Use of off-label and unlicensed drugs in the neonatal intensive care unit and its association with severity scores. J Pediatr (Rio J) 88:465–470Google Scholar
- European Union Pediatric Formulations Initiative. http://www.eupfi.org/. Accessed 19 May 2015
- FP7 LENA. http://www.lena-med.eu/. Accessed 19 May 2015
- Rao SC, Srinivasjois R, Hagan R, Ahmed M (2011) One dose per day compared to multiple doses per day of gentamicin for treatment of suspected or proven sepsis in neonates. Cochrane Database Syst Rev 9:CD005091Google Scholar
- WHO, UNICEF. Make medicines child size. http://www.who.int/childmedicines/media/backgrounder/BG2/en/index.html. Accessed 19 May 2015