In December 2005, on a flight to Brussels, one of us (Francis Mimouni) travelled with Prof. David Branski, of blessed memory, to the board meeting of the European Academy of Pediatrics. David asked Francis if he had any ideas about possible topics for books in the Karger series in Pediatrics. Francis, a neonatologist, immediately felt that one of greatest challenges in Neonatology was the correct use of medications, which for the most part, have never been tested in neonates, and even less so in small, fragile 'micropremies'.
David registered the idea as a 'good one1, and in 2011, he contacted Francis. The problem was that Francis was not a real pharmacologist, and his connection with the 'alchemistry' of drugs was through the field of nutrition and metabolism. Francis promptly looked for a partner for this endeavor and found that the specific issues he thought needed to be tackled were the topics of a newly organized course in Pediatric and Neonatal pharmacology at the European Society for Pediatric Research's annual meeting in Newcastle. Well-respected European and US experts gave outstanding lectures during this course, and Francis met Johannes van den Anker, one of only a handful of world-renowned experts in Neonatal Pharmacology. We decided to work together on this book, which is dedicated to Neonatal Pharmacology and Nutrition, and used the program of the ESPR course as a template. To make it even more attractive for the readership, we have added three very relevant chapters to its content: a chapter on the regulation of drug development, another on the rationale and scientific basis for formula development in preterm infants, and a third chapter presenting a systematic review and meta-analysis on the use of paracetamol (acetaminophen) for the medical closure of patent ductus arteriosus.
We hope you will enjoy reading this book, which is dedicated to the memory of our dear friend, Prof. David Branski. Francis B. Mimouni, Tel Aviv Johannes N. van den Anker, Washington, DC/Basel/Rotterdam

Foreword vi

Preface vii

1 Influence of Maturation and Growth on Drug Metabolism from Fetal to Neonatal to Adult Life 1

2 How to Translate Pharmacokinetic Data into Dosing Recommendations 13

3 Pharmacovigilance in Neonatal Intensive Care 28

4 Neonatal Formulations and Additives 41

5 Modelling and Simulation to Support Neonatal Clinical Trials 58

6 A Systematic Review of Paracetamol and Closure of Patent Ductus Arteriosus: Ready for Prime Time? 70

7 Formulation of Preterm Formula: What's in it, and Why? 83

8 Neonatal Pharmacotherapy: Legal and Regulatory Issues 108

Author Index 124

Subject Index 125

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