Mechanistic modelling of drug target binding kinetics as determinant of the time course of drug action in vivo

Witte, W.E.A. de

Mechanistic modelling of drug target binding kinetics as determinant of the time course of drug action in vivo

Author(s):: Witte, W.E.A. de (0000-0002-0840-3619)

Published: 2017
Publication type: Doctoral Thesis

Abstract

Drug-target binding kinetics determine the time course of

the central event in pharmacotherapy: Drug-target interaction. However, the

time course of a drug effect is also influenced by many other physiological

processes such as the metabolism and excretion of a drug and the transduction of the relevant biological signals. In this study, we investigate when target binding kinetics are determining the time course of drug effect and generate understanding into the relation between the parameter values and the rate-limiting step in the duration of a drug effect.

Binding kineticsDissociation rate constantPKPDModelingRate-limiting steDiscovery

Defense date: 2017-12-19
Language: English
Supervisor(s): Danhof, M.; Graaf, P.H. van der
Advisor(s): Lange, E.C.M. de
Committee member(s): Irth, H.; Bouwstra, J.A.; Charlton, S.J.; Vermeulen, A.; IJzerman, A.P.; Stelt, M. van der; Proost, J.H.
Qualification: Ph.D.
Degree granting institution: Leiden Academic Centre for Drug Research (LACDR), Science, Leiden University, Leiden
hdl: 1887/58472
ISBN(s): 9789463322782

Funding

Sponsorship: The research described in this thesis is part of the K4DD (Kinetics for Drug Discovery) consortium which is supported by the Innovative Medicines Initiative Joint Undertaking (IMI JU) under grant agreement no 115366. The IMI JU is a project supported by the European Union’s Seventh Framework Programme (FP7/2007–2013) and the European Federation of Pharmaceutical Industries and Associations (EFPIA).