In Focus
In Focus
Right time, Right place, Right concentration
Course
Course
5-7th October 2010, Leiden, The Netherlands
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Blood-Brain Barrier in CNS Drug Development: Principles, Transport Kinetics, Diseases & Methods Aim
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This course will address the role and function of the Blood-Brain Barrier (BBB) 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.
Background Only a few CNS diseases can be treated adequately. We are facing an extremely high unmet medical need. Moreover, this problem is getting worse as with our current ageing population the number of people suffering from CNS diseases is growing. Thus, there is a huge market for new CNS drugs. However, the development of new CNS drugs is notoriously difficult. For a proper CNS effect the drug should have the ability to cross the BBB and then to reach the relevant target site within the CNS. This indicates that BBB functionality is of high importance. However, also other factors like plasma pharmacokinetics and intra-brain distribution are of importance. All these factors are all governed by mechanisms which may have intra- and between subject variability. Among many others active transport by P-glycoprotein and binding of the drug to plasma and brain components. Knowledge of the conditional contribution of such mechanisms is of utmost importance for proper CNS drug development and disease treatment.
Who should attend? This course will be of benefit to researchers from Academia, Pharmaceutical Industries, Regulatory Agencies and Contract Research Organizations with a need for better understanding of the BBB and other factors that determine CNS target site distribution of drugs. A general understanding of physiology and minimal knowledge on differential equations is expected (some information can be provided upon request).
Learning Objectives After having taken this course, the participants will have in-depth insight into mechanisms that contribute to BBB transport and intra-brain distribution, with special emphasis on drug delivery and active transport mechanisms know about the driving forces that determine whether or not a CNS drug will be at the right place, at the right time and at the right concentration be able to compare and choose between different methods for studying parameters that can be used to understand or even predict BBB transport and CNS distribution
In Focus Right time, Right place, Right concentration
Course
In Focus
Program
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Tuesday Oct 5th, 2010:
Basic Aspects of the Blood-Brain Barrier Welcome (coffee, tea) Welcome and presentation of course and of participants BBB Morphology, Anatomy, Physiology and Function Break (coffee, tea) BBB Transport Modes (passive, active influx, active efflux, etc) BBB Transport and CNS drug effect Lunch BBB Characteristics and Functionality: Variability in Health and Disease Introduction to Methods that Measure BBB Transport Break (Coffee, tea) Discussions in small groups: Issues in research related to the BBB. General Discussion Dinner
Wednesday, Oct 6th, 2010
Pharmacokinetics of CNS Drug Delivery Problems in CNS drug delivery General Pharmacokinetic (PK) Principles in CNS Drug Delivery Break (coffee, tea) BBB transport. About Rate and Extent. Impact on Brain vs Plasma PK Consequences of (Patho-)Physiological Changes in BBB on Brain vs Plasma PK Lunch Approaches to Overcome Problems in CNS drug delivery Hands-on computer exercises on relationships between plasma and brain PK Coffee and tea available during hands-on Discussion Dinner
Thursday, Oct 7th, 2010
Methods for Investigating BBB Transport In vitro Methods (Cell Cultures, Monolayers) In situ Methods (Brain Uptake, Brain Perfusion, Brain Efflux, IV Injection) Break (coffee, tea) In situ Method (Brain Slice Uptake) In vivo Methods (CSF sampling, Microdialysis) Lunch In vivo Imaging Methods (PET, NMR) What Parameters to Use in CNS Drug Development? Break (coffee, tea) Perspectives and Conclusions Farewell drinks
In Focus Right time, Right place, Right concentration
Course
In Focus
Location
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Het Gravensteen Pieterskerk 6, 2311 SR, Leiden http://www.visitors.leiden.edu/buildings/gravensteen.html “Het Gravensteen” was build in the 13th century. It served als a house for the counts of Holland. In 1463 the city of Leiden took the house in use as a prison. Capital punishments were carried out on the square in front of “het Gravensteen”. In the house one can wittness the many remainders of that time. This “barrier” has opened up: “Het Gravensteen” is currently a monument and used for small conferences, courses and other gatherings. Het Gravensteen (A) is in the City Center of Leiden, at a ~20 min walk distance from Leiden Central Station that has a direct connection to Schiphol Airport (30 min).
In Focus Right time, Right place, Right concentration
Course
Registration
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Registration includes
Course material Drinks and food during the course Dinners Farewell drinks
Limited availability The availability is limited to the number of 35 participants. Registration is effectuated only after receiving registration fee on the basis of first comes first served.
Registration fees Before May 1st 2010
PhD students Academic Business
€ 1395,€ 1495,€ 1695,-
After May 1st and before September 1st 2010
PhD students Academic Business
€ 1695,€ 1755,€ 1995,-
Registration contact For registration use the Regsitration Form. In case of questions please contact Elizabeth de Lange per email (
[email protected]).
In Focus
In Focus Right time, Right place, Right concentration
Course
In Focus
Teachers
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Elizabeth CM de Lange Elizabeth de Lange is Head of the Target Site Equilibration group of the Division of Pharmacology at the LACDR. She obtained her PhD on “The Use of Intracerebral Microdialysis to Study the Blood-Brain Barrier (BBB) Transport Characteristics of Drugs”. Her ultimate aim is to aid in the prediction of the dose-response relationship of CNS drugs in the clinical setting, on the basis of preclinical data (translational research). Her research involves the identification and characterization of the rate and extent key factors in the dose-response relationship of CNS drugs in health and CNS disorders. Dr de Lange’s current research involves the use of intracerebral micro-dialysis, EEG monitoring, and PET scanning. Furthermore advanced mathematical modeling is used to model PKPD relationships and disease progression. Dr de Lange has been the cofounder and (co-)Chair at the 1st, 2nd and 5th of the series of International Symposia on Microdialysis in Drug Research and Development. Furthermore, she is the current Vice Chair of the section “Pharmacokinetics, Pharmacodynamics and Drug Metabolism” (PPDM) of the American Association of Pharmaceutical Scientists (AAPS). She has recently started her company In Focus for training and advice within her area of expertise (microdialysis, PK, PKPD, BBB, and intra-brain distribution).
Margareta Hammarlund-Udenaes Margareta Hammarlund-Udenaes is a Professor in Pharmacokinetics and Pharmacodynamics at Uppsala University. Her research is focused at studying pharmacokinetic aspects of BBB transport of drugs in relation to CNS effects, which has led to the development of new concepts within the BBB transport area, focusing on unbound drug relationships. The concepts make it possible to study the BBB contribution to drug transport to the CNS. A method frequently used is microdialysis, but also PET and other techniques are utilized. Her research group has also optimized in vitro methods for more rapid screening of BBB transport properties in drug discovery. Dr Hammarlund-Udenaes is an Associate Editor of Pharmaceutical Research, and a member of the EAB of the Journal of Pharmaceutical Sciences. She became an AAPS Fellow in 2005 and is a frequent lecturer at drug industry and conferences within the BBB transport - pharmacokinetics area. She cofounded and has co-chaired several of the International Symposia on Microdialysis in Drug Research and Development together with Dr de Lange. The first meeting was held in 1998. Her company Udenaes Consulting gives advice to drug industry in PKPD and BBB transport issues.
In Focus Right time, Right place, Right concentration
Course
Hotels
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http://www.booking.com http://www.sacred-destinations.com/netherlands/leiden-map And in “Google maps” search for : Leiden hotels
