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Blood-Brain Barrier: Drug Transport to the Brain

Vak 2019-2020

This information is without prejudice. Alterations can be made for next year

Description

The development of new drugs with an action on the central nervous system (CNS) is notoriously difficult. For a proper CNS effect, the drug should have the ability to cross the BBB, and then has to find its way to the relevant target site within the CNS. This course will address the role and function of the Blood-Brain Barrier (BBB) and brain tissue distribution in research concerning CNS drug development, CNS drug delivery and CNS diseases. It will provide profound insight in the complex function of the BBB with regard to transport kinetics in health and disease.
The series of lectures will include the following themes:
1. Basic Aspects of the BBB and Pharmacokinetic Principles
2. Principles and Methods for Investigating BBB Transport I
3. Integration and Translation of CNS Drug Delivery Principles
4. Exercises

Coordinator

Mw. Prof. Dr. E.C.M. de Lange

Admission requirements

Students of Bio-Pharmaceutical and Biomedical Sciences or other Life Sciences. Adequate knowledge of parameters that affect local drug concentration, such as drug distribution and clearance.

Mode of instruction

Lectures.

Reading list

• (BOOK) “Drug Delivery to the Brain- Physiological Concepts, Methodologies, and Approaches”. Editors: M. Hammarlund-Udenaes, EC de Lange, and R Thorne. AAPS/ Springer Science and Business Media. 2014; ISBN 978-1-4614-9104-0
• De Lange ECM, Vd Berg DJ, Bellanti F, Voskuyl RA, Syvänen S. P-glycoprotein protein expression versus functionality at the blood-brain barrier using immunohistochemistry, microdialysis and mathematical modeling. Eur J Pharm Sci. 2018 Aug 23;124:61-70. doi: 10.1016/j.ejps.2018.08.022.
• Yamamoto Y, Välitalo PA, Wong YC, Huntjens DR, Proost JH, Vermeulen A, Krauwinkel W, Beukers MW, van den Berg DJ, Hartman RH, Wong YC, Danhof M, Kokkif H, Kokkif M, van Hasselt JGC, de Lange ECM. Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach. Eur J Pharm Sci. 2018 Jan 15;112:168-179.
• De Lange ECM, van der Brink W, Yamamoto Y, de Witte W, Wong YC. Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics. Expert Opin Drug Discov. 2017 Dec;12(12):1207-1218. doi: 10.1080/17460441.2017.1380623. Epub 2017 Sep 21.
• Yamamoto Y, Välitalo PA, Huntjens DR, Proost JH, Vermeulen A, Krauwinkel W, Beukers MW, van den Berg DJ, Hartman RH, Wong YC, Danhof M, van Hasselt JG, de Lange EC. Predicting drug concentration-time profiles in multiple CNS compartments using a comprehensive physiologically-based pharmacokinetic model. CPT Pharmacometrics Syst Pharmacol. 2017 Sep 11. doi: 10.1002/psp4.12250.
• Kervezee L, van der Berg DJ, Hartman RH, Meijer J, de Lange EC. Diurnal variation in the pharmacokinetics and brain distribution of morphine. Eur J Pharm Sci. 2017 May 27. pii: S0928-0987(17)30277-4. doi: 10.1016/j.ejps.2017.05.048
• Yamamoto Y, Danhof M, de Lange EC. Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations. AAPS J. 2017 Mar 9. doi: 10.1208/s12248-017-0050-3

Course objectives

The course will provide profound insight in the complex function of the BBB with regard to transport kinetics in health and disease.

Assessment method

Written exam.

Timetable

February 2020. The specific schedule will be published on Blackboard.

Registration

Application via uSis. Registration closes 14 days before the start of the course or earlier when the maximum number of students is reached.

Remarks

A minimum of 5 participants and a maximum of 60 participants applies to this course. Placement is based on the registration date.