Cover Page
The following handle holds various files of this Leiden University dissertation:
http://hdl.handle.net/1887/81579
Author: Vendel, E.
Title: Prediction of spatial-temporal brain drug distribution with a novel mathematical model
Issue Date: 2019-12-17
537324-L-sub01-os-Vendel 537324-L-sub01-os-Vendel 537324-L-sub01-os-Vendel
537324-L-sub01-os-Vendel Processed on: 24-10-2019Processed on: 24-10-2019Processed on: 24-10-2019Processed on: 24-10-2019
UITNODIGING
voor het bijwonen van de openbare verdediging van
het proefschrift
‘Prediction of spatial- temporal brain drug distribution with a novel
mathematical model’
door Esmée Vendel op dinsdag 17 december
2019 om 13:45 uur in het Academiegebouw van de
Universiteit Leiden, Rapenburg 73 te Leiden.
Na afloop van de verdediging is er een receptie.
Prediction of spatial-temporal brain drug distribution with a
novel mathematical model
Esmée Vendel
Prediction of spatial-temporal brain drug distribution with a novel mathematical model Esmée Vendel
How can we improve the prediction of the local distribution of a drug within the brain?
To address this question, a model is built to study drug distribution within the brain over time and space. The model describes 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. Parameter values are chosen based on values that are known from experimental data. 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.
UITNODIGING
voor het bijwonen van de openbare verdediging van
het proefschrift
‘Prediction of spatial- temporal brain drug distribution with a novel
mathematical model’
door Esmée Vendel op dinsdag 17 december
2019 om 13:45 uur in het Academiegebouw van de
Universiteit Leiden, Rapenburg 73 te Leiden.
Na afloop van de verdediging is er een receptie.
Prediction of spatial-temporal brain drug distribution with a
novel mathematical model
Esmée Vendel
Prediction of spatial-temporal brain drug distribution with a novel mathematical model Esmée Vendel
How can we improve the prediction of the local distribution of a drug within the brain?
To address this question, a model is built to study drug distribution within the brain over time and space. The model describes 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. Parameter values are chosen based on values that are known from experimental data. 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.
UITNODIGING
voor het bijwonen van de openbare verdediging van
het proefschrift
‘Prediction of spatial- temporal brain drug distribution with a novel
mathematical model’
door Esmée Vendel op dinsdag 17 december
2019 om 13:45 uur in het Academiegebouw van de
Universiteit Leiden, Rapenburg 73 te Leiden.
Na afloop van de verdediging is er een receptie.
Prediction of spatial-temporal brain drug distribution with a
novel mathematical model
Esmée Vendel
Prediction of spatial-temporal brain drug distribution with a novel mathematical model Esmée Vendel
How can we improve the prediction of the local distribution of a drug within the brain?
To address this question, a model is built to study drug distribution within the brain over time and space. The model describes 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. Parameter values are chosen based on values that are known from experimental data. 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.
