The need for mathematical modelling of spatial drug distribution within the brain

• Published in: Fluids and barriers of the CNS Vol. 16; no. 1; pp. 12 - 33
• Main Authors: Vendel, Esmée, Rottschäfer, Vivi, de Lange, Elizabeth C M
• Format: Journal Article
• Language: English
• Published: England BioMed Central 16.05.2019; BMC
• Subjects: Animals; Arachnoid - drug effects; Arachnoid - metabolism; Biological Transport - drug effects; Biological Transport - physiology; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain - drug effects; Brain - metabolism; Brain extracellular fluid; Cerebrospinal fluid; Drug metabolism; Drug transport; Extracellular Fluid - drug effects; Extracellular Fluid - metabolism; Fluid flow; Humans; Mathematical modeling; Mathematical models; Models, Theoretical; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - metabolism; Pharmacokinetics; Review; Tissue Distribution - drug effects; Tissue Distribution - physiology; Drug transport; Brain extracellular fluid; Mathematical modeling; Pharmacokinetics; Blood–brain barrier
• ISSN: 2045-8118; 2045-8118
• DOI: 10.1186/s12987-019-0133-x

The blood brain barrier (BBB) is the main barrier that separates the blood from the brain. Because of the BBB, the drug concentration-time profile in the brain may be substantially different from that in the blood. Within the brain, the drug is subject to distributional and elimination processes: diffusion, bulk flow of the brain extracellular fluid (ECF), extra-intracellular exchange, bulk flow of the cerebrospinal fluid (CSF), binding and metabolism. Drug effects are driven by the concentration of a drug at the site of its target and by drug-target interactions. Therefore, a quantitative understanding is needed of the distribution of a drug within the brain in order to predict its effect. Mathematical models can help in the understanding of drug distribution within the brain. The aim of this review is to provide a comprehensive overview of system-specific and drug-specific properties that affect the local distribution of drugs in the brain and of currently existing mathematical models that describe local drug distribution within the brain. Furthermore, we provide an overview on which processes have been addressed in these models and which have not. Altogether, we conclude that there is a need for a more comprehensive and integrated model that fills the current gaps in predicting the local drug distribution within the brain.