Pediatric intensivist & clinical pharmacologist. Erasmus MC Sophia Children s Hospital, Rotterdam, (Netherlands)

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1 Curriculum Vitae PERSONAL INFORMATION Saskia de Wildt WORK EXPERIENCE January 2010 Present Pediatric intensivist & clinical pharmacologist Erasmus MC Sophia Children s Hospital, Rotterdam, (Netherlands) EDUCATION AND TRAINING 1993 Master of Science (M.Sc. Medicine) University of Maastricht, NL, (Netherlands) ADDITIONAL INFORMATION Expertise 2. Academic education and degrees Master of Science (M.Sc. Medicine), University of Maastricht, NL Medical Doctor (M.D.), University of Maastricht, NL Doctorate degree (Ph.D.), Erasmus Universiteit Rotterdam, NL Thesis: Developmental aspects of midazolam metabolism Dutch Board Registration Pediatrician, Erasmus MC Sophia Children s Hospital, NL American Board Registration Clinical Pharmacologist (American Board of Clinical Pharmacology) Dutch Board Registration Clinical Pharmacologist (Dutch Society of Clinical Pharmacology and Biopharmaceutics) Dutch Board Registration Pediatric Intensivist (Erasmus MC Sophia Children s Hospital, NL) Associate Professor (Erasmus MC, Rotterdam NL) 3. Current and previous employment and training since graduating Jan present Jan present Managing Director Medicines for Children Research Network, the Netherlands Pediatric intensivist & clinical pharmacologist (permanent staff) Intensive Care and Pediatric Surgery Erasmus MC Sophia Children s Hospital, Rotterdam, NL Oct Jan 2010 Fellowship Pediatric Intensive Care/Clinical Pharmacology Erasmus MC Sophia Children s Hospital, Rotterdam, NL & the Hospital for Sick Children, Toronto, ON, Canada of which: 2 ½ year Intensive Care fellowship 1 ½ year Clinical Pharmacology fellowship 3 months research April 2001 Oct 2005 Resident Pediatrics (accredited program, the Netherlands) Erasmus MC Sophia Children s Hospital, Rotterdam, NL May 1997 Apr 2001 PhD student (supervisors Prof Dr J.N. van den Anker & Prof Dr Gregory L. Kearns) Thesis Developmental aspects of midazolam metabolism 18/11/14 European Union, Page 1 / 13

2 Department of Pediatrics, Division of Neonatology Erasmus University, Sophia Children s Hospital, Rotterdam, Children s Mercy Hospital, Kansas City, Missouri, USA Mar 1996 May 1997 Jan 1996 Mar 1996 Resident Pediatrics Sint Franciscus Gasthuis, Rotterdam, NL Resident Pediatric Surgery Wilhelmina Children s Hospital, Utrecht, NL 2 4. International experience April 2012 (one month) July 2006-Dec 2006 July 2007-June 2008 (total 18 months) Jan 2007-June 2007 (6 months) Oct-Dec 1997 (3 months) Oct Aug 1993 & Febr-Mrt 2004 (total 13 months) Visiting scientist In vitro drug metabolism/transport studies Division of Clinical Pharmacology, University of Western Ontario, London, ON, Canada. (Prof Dr. Richard B. Kim) Clinical Research Fellow Pediatric Clinical Pharmacology Division of Clinical Pharmacology and Toxicology, the Hospital for Sick Children, Toronto, Canada (Prof Dr Gideon Koren & Prof Dr. Shinya Ito) Clinical Fellow Pediatric Intensive Care Department of Critical Care Medicine, the Hospital for Sick Children, Toronto, Canada (Dr. Peter Cox) PhD student: Visiting student to familiarize with lab techniques for in vitro drug metabolism and drug analysis Department of Clinical Pharmacology,Children s Mercy Hospital, Kansas City, USA (Prof Gregory Kearns) Junior research fellow: Renal effects of ACE inhibition and furosemide in newborn lambs, physiology study, Department of Physiology, University of Calgary, Canada (Dr Francine G. Smith) 5. Honors and awards 2009 Poster Award Dutch Society of Intensive Care (NVIC) (last author), Ede 2009 ASCPT Top Membership Recruiter Best Presentation Award, Research Day, Clinical Pharmacology, Hospital for Sick Children, Toronto 2003 Poster Award, American Society of Clinical Pharmacology and Therapeutics, Orlando between 1992 and 2007: 9 travel awards for international research visits and conferences: Dutch Scientific Organization (NWO), Sophia Foundation for Scientific Research, SWOL University Fund Limburg, Roche, Canadian Society for Clinical Pharmacology, Trust Fund Erasmus University 18/11/14 European Union, Page 2 / 13

3 6. PhD supervision Completed - E. Wildschut, Drug therapy in pediatric patients requiring Extra Corporeal Membrane Oxygentation (ECMO), Erasmus MC Sophia, Intensive Care promoter D. Tibboel, July 2, I. Ceelie, To optimize pain treatment in postoperative pediatric patients Erasmus MC Sophia, Intensive Care, promoter: D. Tibboel, September 30, 2011 Ongoing - I. Ince, Population Pharmacokinetics and Pharmacodynamics of midazolam in children, Erasmus MC Sophia, Intensive Care/Leiden Amsterdam Center for Drug Research, Leiden. TopInstute Pharma project, promotores: D. Tibboel, M. Danhof, planned thesis date, March V.G.J.M. Gijsen, Pharmacogenomics of tacrolimus pharmacokinetics and pharmacodynamics in pediatric transplant patients, Erasmus MC Sophia, Intensive Care, the Hospital for Sick Children, promotores: D. Tibboel, G Koren, planned thesis data March A. Zwiers. Biomarkers for renal toxicity in critically ill children, Erasmus MC Sophia Intensive Care, promoter D. Tibboel, planned thesis date Oct N. Vet, Individualization of sedation in critically ill children, Erasmus MC Sophia, Intensive Care, ZonMW AGIKO, promoter: D. Tibboel, planned thesis date July 2014 M. Mooij. Microdosing in pediatric patients. Erasmus MC Sophia Intensive Care. Promoter D.Tibboel, planned thesis date, Sept 2015 E.Spaans, Identifying the right drug dose in children. Erasmus MC Sophia Intensive Care, planned thesis date June Research grants Year Grants Primary investigator EU FP7 LENA (Workpackage Leader) Labeling of Enalapril from Neonates up to Adolescents EU FP7 GAPP (Workpackage Leader) GAbapentin in Paediatric Pain Investigator-initiated grant Novartis, Basel (PI) In vitro ontogeny of drug transporters 18/11/14 European Union, Page 3 / 13

4 ZonMW Priority Medicines for Kinderen Pediatric microdosing: elucidating age-related changes in oral absorption to guide dosing of new formulations ZonMW Priority Medicines for Kinderen Optimizing sedation in pediatric ICU patients, a nationwide study on efficacy and safety of daily interruption of sedation (copi) Stichting Nuts Ohra Disposition and efficacy of a new rectal omeprazole formulation for gastro-esophageal reflux disease in infants ZonMW Clinical Fellow Pharmacogenetics of tacrolimus-induced nephrotoxicity in pediatric transplant patients Erasmus MC Mrace Clinical Fellowship Pharmacogenetics of tacrolimus-induced nephrotoxicity in pediatric transplant patients ZonMW Agiko (co-pi) Daily sedation interruption in critically ill children PhD candidate: Dr. N. Vet Erasmus MC Doelmatigheid (co-pi) Daily sedation interruption in critically ill children Other personal grants Research Training Competition (Restracomp) Hospital for Sick Children, fellowship ter Meulen Fund, KNAW, research fellowship Optimizing drug therapy in children: tacrolimus in pediatric transplant Research Training Competition (Restracomp) Hospital for Sick Children, fellowship Other grants (co-investigator) ZonMW Priority Medicines voor Kinderen Towards a framework for development and implementation of pediatric oral liquids; amlodipine and lorazepam as proof of concept (PI Dr.L.Hanff) ZonMW PriomedChild Multidisciplinary grant Pain studies in children (PI D. Tibboel/C. Knibbe) Sophia Foundation Scientific Research (SSWO) Biomarkers for AKI in critically ill children (PI D Tibboel, PhD candidate A Zwiers) Top Institute Pharma Population PK-PD of midazolam (PI M.Danhof, Leiden, PhD candidate I. Ince) Erasmus MC Revolving Fund Pharmacogenomics, (PI RHN van Schaik) Amount (Euros) /11/14 European Union, Page 4 / 13

5 Memberships of scientific committees or boards of professional societies (national, international) present present present present present present present present Director-At-Large American Society of Clinical Pharmacology and Therapeutics (ASCPT) Section Chair Special Populations, ASCPT Section Chair Pharmacology, European Society Pediatric Neonatal Intensive Care Member research committee, Society of Critical Care Medicine MCRN representative to Enpr-EMA: European Network of Paediatric Research at the European Medicines Agency Member Research Ethics Board, Erasmus MC Rotterdam Board Member (treasurer) European Society for Developmental Paediatric and Perinatal Pharmacology Committee member Dutch Ministry of Health, Pediatric addendum to Law on Human Research Co-Chair Special Population Section, ASCPT, USA Board member TULIPS (Training Upcoming Leaders in Pediatrics) Rotterdam Medicine for Children Research Network, Amsterdam Chairman Clinical Study Group ICU/pain/anesth Member PK-PD platform Leader Regional Research Center Rotterdam Committee Member ASCPT Membership Action Team, USA Scientific Committee Member Congress Rotterdam 2008 European Society of Developmental Pharmacology Member Opioid Safety Taskforce Hospital for Sick Children, Toronto Member Advisory Board Dutch Pediatric Formulary ledgdutch Dutch Knowledge Center Pharmacotherapy in Children 9. Editorships or memberships of editorial board 18/11/14 European Union, Page 5 / 13

6 2012 Guest editor Special Edition: Obstetric and pediatric pharmacology for Current Drug Metabolism, present Member editorial board: Therapeutic Drug Monitoring Member editorial board: Farmacotherapie bij kinderen 10. Membership of professional societies (since) American Society of Clinical Pharmacology and Therapeutics European Society of Developmental, Perinatal and Pediatric Pharmacology Dutch Society of Pediatrics (NVK) Section of pediatric intensive care (SICK) Canadian Society of Clinical Pharmacology Society of Critical Care Medicine (USA) Dutch Society of Clinical Pharmacology & Biopharmaceutics European Society of Intensive Care Medicine/European Society of Pediatric Neonatal Intensive Care 11. Teaching experience From 2005 present: National Pediatric Residency Curriculum Practical Pediatric Pharmacology (2010) Hospital Pharmacist Curriculum Pharmacology in PICU (2010, 2011) Pharmacy Technician course Developmental Pharmacology (2009) 5 Local - Director Fellowship Program Clinical Pharmacology Erasmus MC - Liasion Rotterdam NIH Clinical Pharmacology Course - Fellows/staff Toronto ICU rounds: Spontaneous peritonitis (2008) - Residents/fellows Rotterdam & Toronto: Pharmacokinetics for the intensivist, recurring Pharmacogenomics, yearly Drugs in lactation (2008) - Medical students Rotterdam: Pediatric Clinical Pharmacology lecture Basic Life Support (2008-9) AKTE (week-long introduction clerkships) - Pharmacy students University of Toronto Immunosuppressants TDM (2008) - Nursing program Erasmus MC (Rotterdam: Rhabdomyolisis, asthma, acid-base regulation, exanthemas, near-drowning, pharmacology - Grand Round Pediatrics (Rotterdam): Pediatric Pharmacology: clinical cases 12. Scientific reviewer for: Clinical Pharmacology and Therapeutics Clinical Pharmacokinetics Critical Care Medicine Pharmacogenomics Journal European Journal of Clinical Pharmacology 18/11/14 European Union, Page 6 / 13

7 Therapeutic Drug Monitoring Clinical Medicine Paediatric Perinatal Drug Therapy Canadian Journal of Clinical Pharmacology British Medical Journal Archives of Diseases of Childhood PLOSOne 13. Scientific presentations invited New developments in paediatric pharmacotherapy - from the bench to the regulator? GMP/DMPG Open Meeting, Paris, Oct Acute liver toxicity: Is it really paracetamol? or how a new biomarker may aid. EAPS 2014, Barcelona, Oct , 2014 Randomized controlled trials in pediatric critical care. Section meeting Intensive Care Kinderen - NVK, Utrecht, June 2014 Can genes predict kidney failure induced by tacrolimus in pediatric transplant patients? New Kids on the Block Dutch Nephrologists, Amsterdam, April 11, 2014 Effects of drugs in critically ill children: Effectiveness and Safety assessment. ISPE, Rotterdam, April 7, 2014 Microdosing in children. A tool to study maturation of pharmacokinetics? American Society of Clinical Pharmacology and Therapeutics, March 2014 Pediatric Pharmacology New developments. Symposium Kinder farmacologie. PAO Heyendaal, Nijmegen, February Drugs in children more than age alone! Symposium 150 jaar Sophia, Rotterdam, November 2013 Medicines for Children Research Network the Dutch Experience. SwissPedNet, Annual meeting. Bern, Switzerland, November 2013 Acute leverfalen bij therapeutische paracetamol dosering. Nederlandse Vereniging voor Kindergeneeskunde. Veldhoven, November Drug metabolism in children: the interplay of age, disease and genetics. Research Rounds. Institut Klinische Farmacologie. Stuttgart, July 2013 Drug-drug interactions in children. ESPNIC Rotterdam. June 6, 2013 Safe and effective use of medicines. Treatment of pain in critically ill patients. ESDPPP Salzburg, June 2013 Hot topics from paediatric drug trials: Pediatric intensive care. ESDPPP Salzburg, June 2013 How do we dose children? TNO Round table Zeist, May 2013 Neonatal Safety of maternal drug therapy. ECCO 13 Vienna, February 2013 Smarter using microdosing in children. ZonMW GGG days, Maarssen. January 2013 Paediatric drugs and doses:the intersection of development and disease. Eckenstein-Geigy Professorship Lecture, UKBB, Basel. November Phenotyping of drug metabolism in children. Pediatric Pharmacogenomics and Personalized Medicine Conference. Kansas City, Missouri. Thursday, March 29, 2012 Geneesmiddelen en borstvoeding: niet altijd zwart wit. Bijwerkingendag Lareb, Utrecht, Nov 24, Medication and the Neonate. Cancer in Pregnancy conference, Leuven, Sept 16, 2011 Does Critical Illness affect Pharmacokinetics and Drug Action in Children?, European Society of Developmental Perinatal Pediatric Pharmacology, Oslo June 15, 2011 De moeder van uw neonaat een geneesmiddel: liever niet? Refereeravond Neonatologie, regio Rotterdam, 26 april 2011 Pharmacotherapie in de zwangerschap. ObNeo congres, Veldhoven, 11 februari, 2011 Off label voorschrijven, formuleringen en kinderen: een goede combi? Apothekers Zeeland, november 18/11/14 European Union, Page 7 / 13

8 25, 2010 Challenges and Solutions for Pediatric Trials. Pharmaceutical Society of Denmark, Nov 24, 2010 Sampling techniques in pediatric drug trials. Sept 2010 Pediatric Pharmacology Meeting, NextlevelPharma, Brussels, Belgium Therapeutic drug monitoring for intensivists. June 2009, ESPNIC, Verona, Italy 6 Immunosuppressants for intensivists. June 2009, ESPNIC, Verona, Italy Pediatric Pharmacology 101. Grand Round Pediatrics. Erasmus MC Sophia, Rotterdam, NL Developmental aspects of midazolam disposition. Motherisk Grand Rounds (CME accredited), 2007 the Hospital for Sick Children, Toronto, NL Personalized dosing of tacrolimus in pediatric transplant patients. Pediatric Transplant Grand Rounds, (CME accredited), 2006, the Hospital for Sick Children,Toronto, NL Personalized dosing of tacrolimus for transplant in critically ill patients. Critical Care Research Rounds (CME accredited), 2006, the Hospital for Sick Children, Toronto, NL Clinical trials in neonates, 4th Workshop on Paediatric Clinical Trials. September 2006, Toronto, Canada Pharmacogenomics of sedation and pain in children. Research Day Pediatric Anesthesiology, 2006, Rotterdam, NL Pharmacogenetics in pediatric intensive care. in TEDDY First Open Conference Brussels, Belgium Developmental aspects of midazolam disposition and effect in neonates, Neonatalogy Grand Rounds, University of Leuven, 2002, Leuven, Belgium Developmental aspects of drug disposition in neonates, Neonatology, Continuous Medical Education, University of Maastricht, 2000, Maastricht, NL Oral presentations plenary International I Ceelie, SN de Wildt, M van Dijk, MM van den Berg, GE van den Bosch, HJ Duivenvoorden, TG de Leeuw, RA Mathot, CA Knibbe, D Tibboel. Intravenous paracetamol reduces morphine requirements in neonates and young infants undergoing major non-cardiac surgery: results of a randomized controlled trial. Clinical Pharmacology & Therapeutics Gijsen VGJM, Koren G, de Wildt SN. The incidence of tacrolimus-induced nephrotoxicity in children: do we really know? ESDPPP 2011, Oslo de Wildt S N, P Yazdani Brojeni, R H N van Schaik, SP Soldin, OP Solding, C ParshuramI Nulman, G Koren. Effect of age and genotype on tacrolimus requirements in pediatric liver and kidney transplant patients. Clinical Pharmacology & Therapeutics de Wildt, S N, D J Murry, G L Kearns, W C J Hop, S Abdel-Rahman, and J N van den Anker, Pharmacokinetics of IV midazolam and 1-OH-midazolam in preterm infants. Clinical Pharmacology & Therapeutics, (2): p. P20-P20. de Wildt, S N, D J Murry, G L Kearns, and J N van den Anker, PK of oral midazolam in preterm infants. Paediatric and Perinatal Drug Therapy, (4): p. 173 (P5). de Wildt, S N, L Riva, J N van den Anker, and D J Murry, Does age alter the pharmacokinetics of midazolam and 1-OH-midazolam in pediatric patients? Clinical Pharmacology & Therapeutics, (2): p de Wildt, S N, M G A Wezenberg, J N Van den Anker, and A G Vulto, Can saliva be used for therapeutic drug monitoring (TDM) of caffeine in preterm infants? Developmental Physiopathology and Clinics, (1 (Suppl)): p National (in dutch) de Wildt, S N, B Delsing, and M Smit. Constipation, a case of Munchhausen by proxy? 1e Interklinische avond Kindergeneeskunde Rotterdam. de Wildt, S N and M de Hoog. Pharmacogenetics in pediatrics, only the beginning. Wetenschapsdag Kindergeneeskunde Erasmus MC Rotterdam. de Wildt, S N, R H N van Schaik, J N van den Anker, and J Lindemans. CYP3A4-V polymorphism: allele frequencies in Dutch Caucasians. in AAV Wetenschapsdag Erasmus MC Rotterdam. 7 18/11/14 European Union, Page 8 / 13

9 de Wildt, S N, G L Kearns, D J Murry, W C J Hop, and J N van den Anker. Developmental aspects of midazolam metabolism. in Mededelingendag Nederlandse Vereniging voor Klinische Farmacologie en Biofarmacie Utrecht. de Wildt, S N, D J Murry, and J N van den Anker, Midazolam pharmacokinetics in preterm infants. Tijdschrift voor Kindergeneeskunde, 2000(Suppl 1): p Sie, S D, S N de Wildt, E van der Giesen, D J Murry, W C J Hop, and J N Van den Anker, Midazolam in preterm infants, a sedative or not? Tijdschrift voor Kindergeneeskunde, 2000(suppl 1): p. 88. Publications International - refereed 1. Zwiers AJ, IJsselstijn H, van Rosmalen J, Gischler SJ, de Wildt SN, Tibboel D, Cransberg K. CKD and Hypertension during Long-Term Follow-Up in Children and Adolescents Previously Treated with Extracorporeal Membrane Oxygenation. Clin J Am Soc Nephrol Oct 2. [Epub ahead of print] (Impact factor 5.3, Q1 upper10). 2. Mooij MG, van Duijn E, Knibbe CA, Windhorst AD, Hendrikse NH, Vaes WH, Spaans E, Fabriek BO, Sandman H, Grossouw D, Hanff LM, Janssen PJ, Koch BC, Tibboel D, de Wildt SN. Pediatric Microdose Study of [(14)C]Paracetamol to Study Drug Metabolism Using Accelerated Mass Spectrometry: Proof of Concept. Clin Pharmacokinet Sep 17. [Epub ahead of print] (Impact factor 5.9, Q1 upper10). 3. de Wildt SN, Tibboel D, Leeder JS. Drug metabolism for the paediatrician. Arch Dis Child Sep 3. [Epub ahead of print] (Impact factor 2.9, Q1) 4. Slooff VD, Spaans E, van Puijenbroek E, Jessurun N, van Beusekom BS, de Hoog M, Tibboel D, de Wildt SN. Adverse events of haloperidol for the treatment of delirium in critically ill children. Intensive Care Med Sep 3. [Epub ahead of print] (Impact factor 5.5, Q1) 5. Matic M, Simons SH, van Lingen RA, van Rosmalen J, Elens L, de Wildt SN, Tibboel D, van Schaik RH. Rescue morphine in mechanically ventilated newborns associated with combined OPRM1 and COMT genotype. Pharmacogenomics Jul;15(10): (Impact factor 3.4, Q1) 6. Boerlage AA, Ista E, Duivenvoorden HJ, de Wildt SN, Tibboel D, van Dijk M. The COMFORT behaviour scale detects clinically meaningful effects of analgesic and sedative treatment. Eur J Pain Jul 29. doi: /ejp.569. [Epub ahead of print] (Impact factor 3.2, Q2) 7. Zwiers AJ, Cransberg K, de Rijke YB, Willemsen SP, de Mol AC, Tibboel D, de Wildt SN. Reference ranges for serum β-trace protein in neonates and children younger than 1 year of age. Clin Chem Lab Med Jun 18. [Epub ahead of print] (Impact factor 2.9, Q1) 8. Mooij MG, Schwarz UI, de Koning BA, Leeder JS, Gaedigk R, Samsom JN, Spaans E, van Goudoever JB, Tibboel D, Kim RB, de Wildt SN. Ontogeny of human hepatic and intestinal transporter gene expression during childhood: age matters. Drug Metab Dispos Aug;42(8): (Impact factor 3.3, Q1) 9. Vet NJ, de Wildt SN, Verlaat CW, Knibbe CA, Mooij MG, Hop WC, van Rosmalen J, Tibboel D, de Hoog M; SKIC (Dutch collaborative PICU research network). Daily interruption of sedation in critically ill children: study protocol for a randomized controlled trial. Trials Feb 13;15(1):55. (Impact factor 2.2, Q3). 10. Zwiers AJ, Cransberg K, van Rosmalen J, Wildschut ED, Tibboel D, de Wildt SN. Loop diuretics are an independent risk factor for acute kidney injury in children on extracorporeal membrane oxygenation with pre-emptive continuous hemofiltration. Intensive Care Med Feb 11. [Epub ahead of print] (Impact factor 5.3, Q1) 11. van Zellem L, Utens EM, de Wildt SN, Vet NJ, Tibboel D, Buysse C. 18/11/14 European Union, Page 9 / 13

10 Analgesia-Sedation in PICU and Neurological Outcome: A Secondary Analysis of Long-Term Neuropsychological Follow-Up in Meningococcal Septic Shock Survivors*. Pediatr Crit Care Med Mar;15(3): (Impact factor 2.2, Q1) 12. Gijsen VM, van Schaik RH, Soldin OP, Soldin SJ, Nulman I, Koren G, de Wildt SN. P450 Oxidoreductase *28 (POR*28) and Tacrolimus Disposition in Pediatric Kidney Transplant Recipients-A Pilot Study. Ther Drug Monit Apr;36(2): (Impact factor 2.2, Q2) 13. Havenaar R, Anneveld B, Hanff LM, de Wildt SN, de Koning BA, Mooij MG, Lelieveld JP, Minekus M. In vitro gastrointestinal model (TIM) with predictive power, even for infants and children? Int J Pharmaceut Nov 30;457(1): (Impact factor 3.8, Q1) 14. Zwiers AJ, de Wildt SN, Hop WC, Dorresteijn EM, Gischler SJ, Tibboel D, Cransberg K. Acute kidney injury is a frequent complication in critically ill neonates on extracorporeal membrane oxygenation: a 14-year cohort study. Crit Care Jul 24;17(4):R151. (Impact factor 4.7, Q1) 15. Gijsen VM, van Schaik RH, Elens L, Soldin OP, Soldin SJ, Koren G, de Wildt SN. CYP3A4*22 and CYP3A combined genotypes both correlate with tacrolimus disposition in pediatric heart transplant recipients. Pharmacogenomics Jul;14(9): (Impact factor 3.9, Q1) 16. Ince I, de Wildt SN, Wang C, Peeters MY, Burggraaf J, Jacqz-Aigrain E, van den Anker JN, Tibboel D, Danhof M, Knibbe CA. A novel maturation function for clearance of the cytochrome P450 3A substrate midazolam from preterm neonates to adults. Clin Pharmacokinet Jul;52(7): (Impact factor 6.1, Q1, Upper10) 17. Ince I, Knibbe CA, Danhof M, de Wildt SN. Developmental changes in the expression and function of cytochrome P450 3A isoforms: evidence from in vitro and in vivo investigations. Clin Pharmacokinet May;52(5): (Impact factor 6.1, Q1, Upper10) 18. Gijsen VM, Hesselink DA, Croes K, Koren G, de Wildt SN. Prevalence of renal dysfunction in tacrolimus-treated pediatric transplant recipients: a systematic review. Pediatr Transplant May;17(3): (Impact factor 1.5, Q2) 19. Ceelie I, de Wildt SN*, van Dijk M, van den Berg MM, van den Bosch GE, Duivenvoorden HJ, de Leeuw TG, Mathôt R, Knibbe CA, Tibboel D. Effect of intravenous paracetamol on postoperative morphine requirements in neonates and infants undergoing major noncardiac surgery: a randomized controlled trial. JAMA Jan 9;309(2): * shared first author. (Impact factor 30, Q1, upper10) 20. van Saet A, de Wildt SN, Knibbe CA, Bogers AJ, Stolker RJ, Tibboel D. The Effect of Adult and Pediatric Cardiopulmonary Bypass on Pharmacokinetic and Pharmacodynamic Parameters. Curr Clin Pharmacol Dec 10. N/A 21. Wildschut ED, de Wildt SN, Mâthot RA, Reiss IK, Tibboel D, Van den Anker J. Effect of hypothermia and extracorporeal life support on drug disposition in neonates. Semin Fetal Neonatal Med Feb;18(1):23-7. (Impact factor 3.5, Q1) 22. Gijsen VM, Madadi P, Dube MP, Hesselink DA, Koren G, de Wildt SN. Tacrolimus-induced nephrotoxicity and genetic variability: A review. Ann Transplant Jun 29;17(2): (Impact factor 0.9, Q4). 23. Buijs EA, Zwiers AJ, Ista E, Tibboel D, de Wildt SN. Biomarkers and clinical tools in critically ill children: are we heading towards tailored drug therapy? Biomark Med Jun;6(3): (Impact Factor, 2,6, Q2). 24. Mooij MG, de Koning BA, Huijsman ML, de Wildt SN. Ontogeny of oral drug absorption processes in children. Expert Opin Drug Metab Toxicol Oct;8(10): (Impact Factor, 3.1, Q2) 25. Ince I, de Wildt SN, Peeters MY, Murry DJ, Tibboel D, Danhof M, Knibbe CA. Critical illness is a major determinant of midazolam clearance in children aged 1 month to 17 years. Ther Drug Monit Aug;34(4): (Impact factor 2.5, Q2). 26. Wildschut ED, Ahsman MJ, Houmes RJ, Pokorna P, de Wildt SN, Mathot RA, Tibboel D. Pharmacotherapy in neonatal and pediatric extracorporeal membrane oxygenation (ECMO). Curr Drug Metab Jul;13(6): (Impact factor 5.1, Q1) 27. Ceelie I, de Wildt SN, de Jong M, Ista E, Tibboel D, van Dijk M. Protocolized post-operative pain management in infants; do we stick to it? Eur J Pain May;16(5): (Impact factor 3,8, Q1) 18/11/14 European Union, Page 10 / 13

11 28. Cella M, Knibbe C, de Wildt SN, Van Gerven J, Danhof M, Della Pasqua O. Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models. Br J Clin Pharmacol Sep;74(3): Feb 2. (Impact factor 3,7 Q1) 29. Vandervaart S, Berger H, Tam C, Goh YI, Gijsen VM, de Wildt SN, Taddio A, Koren G. The effect of distant reiki on pain in women after elective Caesarean section: a double-blinded randomised controlled trial. BMJ Open Jan 1;1(1):e (Impact Factor: N/A) 30. Gijsen VMGJ, Mital S, van Schaik RHN, Soldin OP, Soldin SJ, van der Heiden IP, Nulman I, Koren G, de Wildt SN. Age and CYP3A5 genotype affect tacrolimus dosing requirements after transplant in pediatric heart recipients. J Heart Lung Transp, 2011 Dec;30(12):1352-9, (impact factor 3,4, Q1) 31. Vandervaart S, Berger H, Sistonen J, Madadi P, Matok I, Gijsen VM, de Wildt SN, Taddio A, Ross CJ, Carleton BC, Hayden MR, Koren G. CYP2D6 Polymorphisms and Codeine Analgesia in Postpartum Pain Management: A Pilot Study. Ther Drug Monit Aug;33(4): (impact factor 3.1, Q1) 32. Hoppu K, Anabwani G, Garcia-Bournissen F, Gazarian M, Kearns GL, Nakamura H, Peterson RG, Sri Ranganathan S, de Wildt SN. The status of paediatric medicines initiatives around the worldwhat has happened and what has not? Eur J Clin Pharmacol Jan;68(1):1-10 (impact factor 3.0, Q2) 33. de Wildt SN, van Schaik RH, Soldin OP, Soldin SJ, Brojeni PY, van der Heiden IP, Parshuram C, Nulman I, Koren G. The interactions of age, genetics, and disease severity on tacrolimus dosing requirements after pediatric kidney and liver transplantation. Eur J Clin Pharmacol Dec;67(12): (impact factor 3.0, Q2) 34. de Wildt SN. Profound changes in drug metabolism enzymes and possible effects on drug therapy in neonates and children. Expert Opin Drug Metab Toxicol Aug;7(8): (Impact factor 3.4, Q2) 35. Ceelie I, James LP, Gijsen V, Mathot RA, Ito S, Tesselaar CD, Tibboel D, Koren G, de Wildt SN. Acute liver failure after recommended doses of acetaminophen in patients with myopathies. Crit Care Med 2011 Apr;39(4): (impact factor 6.2, Q1 upper10) 36. Vet NJ, de Hoog M, Tibboel D, de Wildt SN. The effect of inflammation on drug metabolism: a focus on pediatrics. Drug Discov Today May;16(9-10): (impact factor 6.6, Q1 upper10) 37. Ceelie I, van Dijk M, Bax NM, de Wildt SN, Tibboel D. Does minimal access major surgery in the newborn hurt less? An evaluation of cumulative opioid doses. Eur J Pain Jul;15(6): ( (impact factor 3.6, Q1) 38. Vet NJ, de Hoog M, Tibboel D, de Wildt SN. The effect of critical illness and inflammation on midazolam therapy in children. Pediatr Crit Care Med 2012 Jan;13(1):e48-50 (impact factor 2.8, Q1) 39. Wildschut ED, Hanekamp MN, Vet NJ, Houmes RJ, Ahsman MJ, Mathot RA, de Wildt SN, Tibboel D. Feasibility of sedation and analgesia interruption following cannulation in neonates on extracorporeal membrane oxygenation. Intensive Care Med Sep;36(9): (impact factor 5.2, Q1) 40. Ceelie I, van der Starre C, Tibboel D, Stol K, Koren G, de Wildt SN. Evaluation of drug formularies for pediatric intensive care. Ped Crit Care Med, Jan;12(1):e14-9 (impact factor 2.8, Q1) 41. van dervaart S, Gijsen VM, de Wildt SN, Koren G. A systematic review of the therapeutic effects of Reiki. J Altern Complement Med Nov;15(11): (impact factor 1.6, Q2) 42. de Wildt SN, GL Kearns, DJ Murry, G Koren, JN van den Anker. Ontogeny of midazolam glucuronidation in preterm infants. Eur J Clin Pharmacol, 2010 Feb;66(2): (impact factor 1,8, Q2). 43. van der Lee R, Ceelie I, de Wildt SN,Morphine-induced muscle rigidity in a term neonate. Ann Pharmacother Oct;43(10): (impact factor 2, Q2). 44. de Wildt SN, Taguchi N, Koren G. Unintended pregnancy during radiotherapy for cancer. Nat Clin Pract Oncol Mar;6(3): (impact factor 9.1, Q1 upper 10) 45. Ince I, de Wildt SN, Tibboel D, Danhof M, Knibbe CA. Tailor-made drug treatment for children: creation of an infrastructure for data-sharing and population PK-PD modeling. Drug Discov Today Mar;14(5-6): (impact factor 6.6, Q1 upper 10) 46. Gijsen, VM, de Wildt SN, Ito S. The probability of rash as adverse event related to gabapentin therapy in a child. Ann Pharmacother 2009 Feb;43(2):387-9 (impact factor 2, Q1) 47. de Wildt SN, S Ito, G Koren. Challenges for drug studies in children: CYP3A phenotyping as example. Drug Discovery Today, 2009 Jan;14(1-2):6-15. (impact factor 6.6, Q1 upper10) 48. de Wildt S N, R Verzijden, J N van den Anker and M de Hoog. Information technology cannot 18/11/14 European Union, Page 11 / 13

12 guarantee patient safety. BMJ. 2007, 334(7598):851-2 (impact factor: 9.2, Q1 upper10) 49. de Wildt, S N, M J Berns and J N van den Anker. 13C-erythromycin breath test as a noninvasive measure of CYP3A activity in newborn infants: a pilot study. Ther Drug Monit, (2): (impact factor: 2.4, Q1) 50. de Wildt, S N, M de Hoog, A A Vinks, K F Joosten, M van Dijk, and J N van den Anker, Pharmacodynamics of midazolam in pediatric intensive care patients. Ther Drug Monit, (1): p (impact factor: 3.0, Q1) 51. de Wildt, S N, Johnson, T.N., Choonara, I., The effect of age on drug metabolism. Paed Perinat Drug Metab, (3): p , (impact factor: NA) 52. de Wildt, S N, Kearns, G.L., Sie, S.D., Hop, W.C.J., van den Anker, J.N., Pharmacodynamics of intravenous and oral midazolam in preterm infants. Clin Drug Invest, (1): p (impact factor: 0.9, Q3) 53. de Wildt, S N, M de Hoog, A A Vinks, E van der Giesen, and J N van den Anker, Population pharmacokinetics and metabolism of midazolam in pediatric intensive care patients. Crit Care Med, (7): p (impact factor: 4.2, Q1 upper10) 54. de Wildt, S N, G L Kearns, W C Hop, D J Murry, S M Abdel-Rahman, and J N van den Anker, Pharmacokinetics and metabolism of oral midazolam in preterm infants. Br J Clin Pharmacol, (4): p (impact factor: 3.6, Q2) 55. van Schaik, R H, S N de Wildt, R Brosens, M van Fessem, J N van den Anker, and J Lindemans, The CYP3A4*3 allele: is it really rare? Clin Chem, (6): p (impact factor: 4.6, Q1, upper10) 56. de Wildt, S N, K T Kerkvliet, M G Wezenberg, S Ottink, W C Hop, A G Vulto, and J N van Den Anker, Use of saliva in therapeutic drug monitoring of caffeine in preterm infants. Ther Drug Monit, (3): p (impact factor: 2.0, Q1) 57. de Wildt, S N, G L Kearns, W C Hop, D J Murry, S M Abdel-Rahman, and J N van den Anker, Pharmacokinetics and metabolism of intravenous midazolam in preterm infants. Clin Pharmacol Ther, (6): p (impact factor: 5.1, Q1, upper10) 58. van Schaik, R H, S N de Wildt, N M van Iperen, A G Uitterlinden, J N van den Anker, and J Lindemans, CYP3A4-V polymorphism detection by PCR-restriction fragment length polymorphism analysis and its allelic frequency among 199 Dutch Caucasians. Clin Chem, (11): p (impact factor: 4.6, Q1, upper10) 59. de Wildt, S N, G L Kearns, J S Leeder, and J N van den Anker, Glucuronidation in humans. Pharmacogenetic and developmental aspects. Clin Pharmacokinet, (6): p (impact factor: 5.1, Q1, upper10) 60. de Wildt, S N, G L Kearns, J S Leeder, and J N van den Anker, Cytochrome P450 3A: ontogeny and drug disposition. Clin Pharmacokinet, (6): p (impact factor: 5.1, Q1,upper10) 61. Smith, F G, S Chan, and S N de Wildt, Effects of renal denervation on cardiovascular and renal responses to ACE inhibition in conscious lambs. J Appl Physiol, (2): p (impact factor: 1.3, Q2) 62. de Wildt, S N and F G Smith, Effects of the angiotensin converting enzyme (ACE) inhibitor, captopril, on the cardiovascular, endocrine, and renal responses to furosemide in conscious lambs. Can J Physiol Pharmacol, (4): p (impact factor: 1.3, Q2) 63. Smith, F G, A M Strack, and S N de Wildt, Renal nerves do not modulate the renal and endocrine responses to furosemide in conscious lambs. Can J Physiol Pharmacol, (5): p (impact factor: 1.3, Q2) National (refereed) journals 1. Knibbe CA, Tibboel D, de Wildt SN, de Hoog M, Tjoeng MM, Danhof M. [Individualized dosing guidelines for children]. Ned Tijdschr Geneeskd. 2013;157(16):A4214. Review. Dutch. PubMed PMID: Nauta M, M Landsmeer, SN de Wildt [NSAIDs are safe during lactation]. Tijdschr Farmacother Kind, 2010; (3). 3. Landsmeer, M, M Nauta, B te Winkel, SN de Wildt [Are drugs and breastfeeding a safe combination?]. Tijdschr Farmacother Kind; 2009 (2). 4. Bestebreurtje P, Knibbe CAJ, Wildt SN de, van Sorge AA, Tibboel D [Rectal formulation of omeprazole for children younger than 6 months of age with pathological reflux]. Pharm Weekbl 2007;142(20): /11/14 European Union, Page 12 / 13

13 5. Rademaker, C M A, Hanff, L.M., de Wildt, S N, van den Anker, J.N., Vulto, A.G., Schobben, A.F.A.M., [Correct dosing of medications in children]. Pharm Weekbl, : p van Schaik, R H N, de Wildt, S N, Lindemans, J., [Cytochrome P450-polymorphisms and treatmen of cancer]. Ned Tijdschr Clin Chem, : p Kerkvliet, C T M, Wezenberg, M.G.A., de Wildt, S N, Hop, W.C.J., van den Anker, J.N., Vulto, A.G., [Determination of caffeine in saliva as alternative to plasma in preterm infants]. Pharm Weekbl, (42): p van den Anker, J N and S N de Wildt, [Excessive terfenadine level due to drinking grapefruit juice]. Ned Tijdschr Geneeskd, (41): p de Wildt, S N and J N van den Anker, [Syncopes with simultaneous use of terfenadine and itraconazole]. Ned Tijdschr Geneeskd, (36): p (Contributions to) books 1. de Koning BAE, Mooij M, Johnson TN, de Wildt SN Developmental changes in the processes governing drug absorption (editors: Daniel Bar-Shalom, Klaus Rose). 2014: p de Wildt SN, HCJ Scheepers. [Borstvoeding en geneesmiddelen rond de partus]. In: [Een professionele kijk op borstvoeding] (editors: E.J. Anten-Kools, J.P. van Wouwe, A.M. Oudesluys- Murphy, B.A. Semmekrot). 2011: p Ahsman, MJ, D Tibboel, RAA Mathot, SN de Wildt. Chapter: Sample collection, biobanking and analysis. In Pediatric Pharmacology (editors M Schwab), in Human Experimental Pharmacology, 2011;205: Ceelie, I, S N de Wildt, M van Dijk, D Tibboel. How to optimize the treatment of acute pain in nonverbal children. Pediatric Clinical Research Manual, 2008, 4, S de Wildt, S N, I Choonara, and T N Johnson, The effect of age on drug metabolism, in Pediatric Clinical Pharmacology, Choonara I.and Jacqz-Aigrain, Editors, 2006, Informa Healthcare. 6. de Wildt, S N, Johnson, T.N., Choonara, I., The effect of age on drug metabolism. Introduction to Paediatric and Perinatal Drug Therapy, I Choonara, Editor. 2003, Nottingham University Press: Nottingham. p Other 1. Letter: Spaans E, Roofthooft D, de Wildt SN. What gets lost in translation WHO report: Wildschut ED, Vet NJ, de Wildt SN. Application to Add Midazolam to the Model List of Essential Medicines. (result: Midazolam included in Model List of Essential Medicines during 18th Expert Committee on the Selection and Use of Essential Medicines, March 2011) Projects see Expertise Memberships American Society of Clinical Pharmacology and Therapeutics European Society of Developmental, Perinatal and Pediatric Pharmacology Dutch Society of Pediatrics (NVK) Section of pediatric intensive care (SICK) Society of Critical Care Medicine (USA) Dutch Society of Clinical Pharmacology & Biopharmaceutics European Society of Intensive Care Medicine/European Society of Pediatric Neonatal Intensive Care Other Relevant Information 18/11/14 European Union, Page 13 / 13

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