Abstract
PurposeWe have developed a 3D brain unit network model to understand the spatial-temporal distribution of a drug within the brain under different (normal and disease) conditions. Our main aim is to study the impact of disease-induced changes in drug transport processes on spatial drug distribution within the brain extracellular fluid (ECF).MethodsThe 3D brain unit network consists of multiple connected single 3D brain units in which the brain capillaries surround the brain ECF. The model includes the distribution of unbound drug within blood plasma, coupled with the distribution of drug within brain ECF and incorporates brain capillaryblood flow, passive paracellular and transcellular BBB transport, active BBB transport, brain ECF diffusion, brain ECF bulk flow, and specific and nonspecific brain tissue binding. All of these processes may change under disease conditions.ResultsWe show that the simulated disease-induced changes in brain tissue characteristics significantly affect drug concentrations within the brain ECF.ConclusionsWe demonstrate that the 3D brain unit network model is an excellent tool to gain understanding in the interdependencies of the factors governing spatial-temporal drug concentrations within the brain ECF. Additionally, the model helps in predicting the spatial-temporal brain ECF concentrations of existing drugs, under both normal and disease conditions.
Highlights
Insight into the spatial-temporal distribution of a drug within the brain is still limited, but very important for improved understanding of drug interaction with binding sites and drug effects and side effects
In order to increase our understanding of drug distribution within the brain in health and disease conditions, we have developed a 3D network of single brain units that includes the brain capillary blood flow, passive and active blood-brain barrier (BBB) transport, diffusion, brain extracellular fluid (ECF) bulk flow and binding kinetics
We study the effects of brain capillary density, BBB transport, brain ECF diffusion and binding site density on drug distribution within the 3D brain unit network
Summary
Insight into the spatial-temporal distribution of a drug within the brain is still limited, but very important for improved understanding of drug interaction with binding sites and drug effects and side effects. The BBB has great impact on the relationship between drug concentration-time profiles (pharmacokinetics; PK) within the blood plasma and the brain ECF There is a lack of understanding of the mechanisms that may lead to local differences of brain ECF PK. Drug distribution within the brain ECF is governed by many factors, including blood plasma PK in the brain capillaries, BBB transport, diffusion, brain ECF bulk flow as well as by specific and non-specific binding, as reviewed in [2]. All of these factors may be locally different, for example by disease. Brain capillary density may increase as a consequence of certain brain
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
