Cover Page
The handle http://hdl.handle.net/1887/84695 holds various files of this Leiden University dissertation.
Author: Wijk, R.C. van
Title: Translational pharmacokinetics-pharmacodynamics in zebrafish: integration of
experimental and computational methods
Translational
pharmacokinetics-pharmacodynamics in zebrafish:
integration of experimental and
computational methods
It takes two to translate
Cover design and printing: GVO Printers and Designers B.V., Ede, The Netherlands ISBN: 978-94-6332-594-3
The research described in this thesis was performed at the Systems Biomedicine and Pharmacology division of the Leiden Academic Centre for Drug Research (LACDR), Leiden University (Leiden, The Netherlands), and at the Animal Sciences and Health division of the Institute of Biology Leiden (IBL), Leiden University (Leiden, The Netherlands).
© R.C. van Wijk, 2020
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden,
op gezag van Rector Magnificus prof. mr. C.J.J.M. Stolker,
volgens besluit van het College voor Promoties
te verdedigen op donderdag 6 februari 2020
klokke 16:15 uur
door
Rob Christiaan van Wijk
geboren te Zevenaar, Nederland
op 30 juni 1991
Translational
pharmacokinetics-pharmacodynamics in zebrafish:
integration of experimental and
computational methods
Promotores:
Prof. dr. P.H. van der Graaf
Prof. dr. H.P. Spaink
Copromotor:
Dr. E.H.J. Krekels
Promotiecommissie:
Prof. dr. H. Irth, voorzitter
Prof. dr. J.A. Bouwstra, secretaris
Prof. dr. U.S.H. Simonsson
Uppsala University
Prof. dr. J. Gabrielsson
Swedish University of Agricultural Sciences
Prof. dr. J. den Hertog
Hubrecht Institute, KNAW
Prof. dr. ir. F.J. Verbeek
Table of content
SECTION I INTRODUCTION TO HIGH-THROUGHPUT EXPERIMENTATION IN WHOLE VERTEBRATES
Chapter 1 General introduction and scope 9
Chapter 2 Systems pharmacology of hepatic metabolism in zebrafish larvae 15 Chapter 3 Outside-in systems pharmacology combines innovative computational
methods with high-throughput whole vertebrate studies
25 Chapter 4 Multi-modal 3D reconstruction and measurements of zebrafish
larvae and its organs using axial-view microscopy
31
SECTION II QUANTIFICATION OF INTERNAL EXPOSURE OVER TIME
Chapter 5 Pharmacokinetic modelling of paracetamol uptake and clearance in zebrafish larvae: expanding the allometric scale in vertebrates with five orders of magnitude
43
Chapter 6 Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae
57 Chapter 7 Mechanistic and quantitative understanding of pharmacokinetics in
zebrafish larvae through nanoscale blood sampling and metabolite modelling of paracetamol
73
SECTION III LINKING INTERNAL EXPOSURE TO DISEASE DYNAMICS
Chapter 8 Quantification of internal exposure of isotretinoin and neuroblastoma tumour size over time in the zebrafish disease model
101
SECTION IV MECHANISTIC AND QUANTITATIVE TRANSLATION OF EXPOSURE-RESPONSE FROM ZEBRAFISH TO HIGHER VERTEBRATES
Chapter 9 Quantification of natural growth of two strains of Mycobacterium
marinum for translational anti-tuberculosis drug development
125 Chapter 10 Translational pharmacokinetics-pharmacodynamics of isoniazid in
the zebrafish larva tuberculosis disease model
135
SECTION V SUMMARY, DISCUSSION, AND CONCLUSION
Chapter 11 Summary, discussion, and conclusion 165
Chapter 12 Nederlandse samenvatting 185
SECTION VI APPENDICES
Curriculum vitae and list of publications 208
Affiliations of authors 210
