Prediction of spatial-temporal brain drug distribution with a novel mathematical model

Leiden Repository

Prediction of spatial-temporal brain drug distribution with a novel mathematical model

Type: Doctoral Thesis
Title: Prediction of spatial-temporal brain drug distribution with a novel mathematical model
Author: Vendel, E.
Issue Date: 2019-12-17
Keywords: Mathematical model
Drug distribution
Brain extracellular fluid
Drug binding
Drug transport
Pharmacokinetics
Abstract: A novel mathematical model describes spatial-temporal drug distribution within one or more brain units, which are cubic representations of a piece of brain tissue with brain capillaries at the edges. The brain unit can be considered a highly representative building block of the brain in terms of drug distribution. While the focus of the model is on drug distribution within the brain ECF, the model includes descriptions of drug concentrations within the blood plasma, drug distribution via brain capillary blood flow, drug transport across the blood-brain barrier (BBB) by passive paracellular and transcellular transport as well as active transport, brain ECF diffusion, brain ECF bulk flow, non-specific binding of the drug to brain tissue, and drug target binding kinetics. We study the model with analytical methods and numerical simulations. This allows us to examine the integrated effect of the individual processes important to drug distribution and effect on the local concentration-time profiles of free and (non-)specifically bound drug. Moreover, the model allows us to generate a local distribution profile of a drug within the brain. In addition, the impact of disease-induced changes in brain-specific properties on the concentrations of drug within the brain ECF is assessed.
Promotor: Supervisor: Merks R.M.H., Lange E.C.M. de Co-Supervisor: Rottschäfer V.
Faculty: Science
University: Leiden
Uri: urn:isbn:9789402817959
Handle: http://hdl.handle.net/1887/81579
 

Files in this item

Description Size View
application/pdf Full Text 25.22Mb Under embargo until 2021-06-17
application/pdf Cover 7.243Mb View/Open
application/pdf Title Page_Contents 156.9Kb View/Open
application/pdf Chapter 01 2.780Mb View/Open
application/pdf Chapter 02 3.342Mb View/Open Full text at publisher site
application/pdf Chapter 03 9.761Mb View/Open Full text at publisher site
application/pdf Chapter 04 6.821Mb Under embargo until 2021-06-17
application/pdf Chapter 05 3.627Mb Under embargo until 2021-06-17
application/pdf Chapter 06 1.050Mb View/Open
application/pdf References 315.8Kb View/Open
application/pdf Propositions 137.7Kb View/Open

This item appears in the following Collection(s)