Tamara van Donge

Table of contents Part I General introduction Chapter 1 Introduction into quantitative clinical pharmacology and pediatrics 11 Chapter 2 Clinical pharmacology and pharmacometrics to better understand physiological changes during pregnancy and neonatal life 23 Part II Pharmacometric modeling to optimize dosing in neonates Chapter 3 Key components for antibiotic dose optimization of sepsis in neonates and infants 41 Chapter 4 Amoxicillin dosing regimens for the treatment of neonatal sepsis: balancing efficacy and neurotoxicity 59 Chapter 5 Methadone dosing strategies in preterm neonates can be simplified 75 Chapter 6 A novel strategy to personalize use of ibuprofen for closure of patent ductus arteriosus in preterm neonates 97 Part III Pediatric kidney function and injury biomarkers Chapter 7 Characterizing dynamics of serum creatinine and creatinine clearance in extremely low birth weight neonates during the first six weeks of life 125 Chapter 8 Creatinine trends to detect ibuprofen-related maturational adverse drug events in neonatal life: a simulation study for the ELBW newborn 151 Chapter 9 Age-dependent changes of kidney injury biomarkers in pediatrics 165 Chapter 10 Age appropriate reference intervals for eight serum kidney biomarkers in healthy infants, children and adolescents 193 Part IV Discussion and summary Chapter 11 General discussion and future perspectives 229 Chapter 12 Summary 243 Part V Appendices Affiliations of co-authors 251 PhD portfolio 257 List of publications 263 About the author 269 Acknowledgements 273