Elizabeth CM de Lange, Editorial Board Member
Leiden University, Netherlands
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Elizabeth CM de Lange (PhD, Ass Prof) is head of the Target Site Equilibration Group within the Division of Pharmacology at the Leiden/Amsterdam Center for Drug Research.
Elizabeth de Lange’s 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). Such prediction is currently still difficult as often a complex relationship between dose and response of CNS drugs exists, as the factors on the causal chain between drug dosing and CNS effect may vary in rate and extent, in time, by subject, by disease condition, by genetic background, by age, etc. This indicates that there is a need for studies designed to unravel the underlying mechanisms and interspecies similarities and differences in terms of rate and extent.
To that end her current research program involves the identification and characterization of key factors in the dose-response relationship of CNS drugs: the pharmacokinetics of the drug in plasma; the kinetics of passive and active drug transport across the BBB and BCSFB; the kinetics of drug distribution into different compartments in the CNS (such as the extracellular and intracellular spaces, as well as the cerebrospinal fluid), the kinetics of drug equilibration to the target site and the ability of the drug to interact with the target to activate signal transduction pathways that lead to the effect. Also changes in BBB functionality that may occur in CNS disorders, such as Parkinson’s Disease and Epilepsy, are included.
In this research intracerebral microdialysis is used to determine the time course of drug as well as biomarker concentrations in brain extracellular fluid, in combination with other techniques such as serial blood sampling, brain tissue sampling, EEG monitoring, and PET scanning. Advanced mathematical modelling is used to model pharmacokinetic-pharmacodymanic relationships and disease progression.
Elizabeth de Lange was the cofounder and (co-)Chair at the 1rst, 2nd and 5th of the series of International Symposia on Microdialysis in Drug Research and Development. She has been the co-chair of the 11th International Symposium on Signal transduction in the Blood-Brain Barriers, Amsterdam, the Netherlands, Sep 2008. She is currently chair of the organizing committee of the 9th International Conference on Cerebral Vascular Biology (CVB), to be held in June 2011, Leiden, The Netherlands.
As a director of Pharmacokinetic Studies, she has been instrumental in raising the pharmacokinetic microdialysis branch at Brains On-Line in Groningen, The Netherlands. Furthermore, she is a member of the Editorial Advisory Board of the Journal of Pharmaceutical Sciences, and regular reviewer of also other high impact journals.
Elizabeth de Lange has served as steering committee member, incoming Chair, Chair and past Chair of the Microdialysis Focus Group of the American Association of Pharmaceutical Sciences (AAPS). Last year she served as Vice-chair and current Chair-elect of the AAPS section “Pharmacokinetics, Pharmacodynamics and Drug Metabolism” (PPDM).