The 'free drug hypothesis' : fact or fiction?
Steeg, T.J. van
Citation
Steeg, T. J. van. (2008, November 26). The 'free drug hypothesis' : fact or fiction?. Retrieved from https://hdl.handle.net/1887/13283
Version: Corrected Publisher’s Version License:
Licence agreement concerning inclusion of doctoral thesis in the Institutional Repository of the University of Leiden
Downloaded from: https://hdl.handle.net/1887/13283
Note: To cite this publication please use the final published version (if applicable).
The ‘free drug hypothesis’: Fact or fiction?
Proefschrift
ter verkrijging van
de graad van Doctor aan de Universiteit Leiden, op gezag van Rector Magnificus prof.mr. P.F. van der Heijden,
volgens besluit van het College voor Promoties te verdedigen op woensdag 26 november 2008
klokke 11:15 uur
door
Tamara Jessica van Steeg
geboren te Oud-Beijerland in 1978
Promotiecommissie
Promotor : Prof. Dr. M. Danhof Co-promotor : Dr. E.C.M. de Lange Referent : Dr. J.H. Proost
(Rijks Universiteit, Groningen) Overige leden :Prof. Dr. A.F. Cohen
Prof. Dr. E.R. de Kloet
Prof. Dr. A.P. Ijzerman
Prof. Dr. H.J. Guchelaar
Prof. Dr. J.A. Bouwstra
"God, grant me the serenity to accept the things I cannot change, the courage to change the things I can, and the wisdom to know the difference."
(Reinhold Niebuhr)
Aan Jesca, Danique en ?
The research described in this thesis was performed at the division of pharmacology of the Leiden/Amsterdam Center for Drug Research, Leiden University.
The printing of this thesis was financially supported by:
LAP&P consultants B.V., Leiden, The Netherlands
Pfizer Ltd, Research and Development, Sandwich, United Kingdom
Section I - General introduction
Chapter 1 Scope and outline of thesis
Chapter 2 The ‘free drug hypothesis’ in pharmacodynamics: theoretical evaluation of the role of plasma protein binding
Section II - Mechanism-based PKPD modelling of β-blockers
Chapter 3 Pharmacokinetic-Pharmacodynamic modelling of S(-)-atenolol in rats:
Reduction of isoprenaline-induced tachycardia as a continuous pharmacodynamic enpoint
Chapter 4 Mechanism-based pharmacodynamic modelling of S(-)-atenolol:
Estimation of in vivo affinity for the β1-adrenoceptor with an agonist- antagonist interaction model
Chapter 5 Mechanism-based PKPD modelling of β-adrenoceptor antagonists:
Role of plasma protein binding Section III - Challenging the ‘free drug hypothesis’
Chapter 6 Reproducible and time-dependent modification of serum protein binding in Wistar Kyoto rats
Chapter 7 Challenging the ‘free drug hypothesis’: Mechanism-based PKPD modelling of altered AGP binding on heart rate effects of S(-)-propranolol in rats
Section IV - Summary, conclusions & perspectives
Chapter 8 Challenging the ‘free drug hypothesis’ - summary, conclusions &
perspectives
Nederlandse samenvatting (Synopsis in Dutch) Nawoord
Curriculum vitae List of publications
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