Leiden University
Divison of Pharmacology
Leiden/Amsterdam Center for Drug Research (LACDR)
Einsteinweg 55
23333 CC Leiden

The Netherlands

 Homepage

Project Leader

Dr. Elizabeth De Lange Phone: +31-(0)71 527 6330  Fax: +31-(0)70 514 1260  Contact

Project Staff

Dr. Rob Voskuyl Co-project leader  Phone: +31-(0)71 527 6813  Fax: +31-(0) 71 527 6292  Contact

Dr. Stina Syvänen Postdoctoral Fellow  Phone: +31-(0)71 527 6268  Fax: +31-(0) 71 527 6292  Contact

Dr. Louise Van der Weerd Senior Investigator  Phone: +31-(0) 71 526 9307  Contact

BSc Maarten Schenke Biotechnician  Phone: +31-(0) 71 527 6071  Fax: +31-(0)71 527 6292  Contact

BSc Robin Hartman Biotechnician  Phone: +31-(0) 71 5276163  Fax: +31-(0) 71 527 6292  Contact

Institute Presentation

The research at the Division of Pharmacology of Leiden/Amsterdam Center for Drug Research (LACDR), University Leiden,  focuses on the development of novel theoretical concepts of mechanism-based PK-PK models (synonymous with “Biological Systems analysis”). It constitutes the scientific basis for prediction of drug effects in humans. Important contributions have been the incorporation of receptor theory and dynamical systems analysis in PK-PD modelling. A more recent development is the focus on modelling of disease processes (both clinically and pre-clinically).
Specific attention is given to: i) the degree of protein binding in plasma, ii) the mechanisms and kinetics of transport across the blood-brain barrier (BBB), iii) the interaction with the specific receptors in the brain and iv) the influence of CNS disorders.

Specifically of  importance with regard to the EURIPIDES consortium our Division has ample experience with research on  epilepsy and pharmacoresistance, with studies performed in rat models with cortical stimulation and kindling, and rat models of absence epilepsy and pharmacoresistance. Issues like chronic medication and rational combinations  of antiepileptic drugs were addressed, as well as changes in GABAA-mediated inhibition in pharmacoresistance and identification of biomarkers for disease progression in epilepsy.
With regard to blood-brain barrier (BBB) functionality and brain distribution of drugs microdialysis represents an important tool to monitor brain extracellular (free) drug concentrations. Many projects have included this technique and unequivocally demonstrated that intracerebral microdialysis provides meaningful information on drug transport to the brain. For example, the Impact of P-glycoprotein efflux in BBB transport has been studied by comparing mdr1a(-/-) with wild-type mice, as well as the impact of BBB transport on the relation between plasma pharmacokinetics and CNS effects.
Also, microdialysis has been applied in rat models of epilepsy and pharmacoresistance to contribute to unravelling the potential changes in BBB functionality by different factors of epilepsy.

Most recently, in collaboration with G. Luurtsema, (Nuclear Medicine & PET research, VU Medical Center (VuMC), Amsterdam), feasibility studies in a small number of rats were performed to obtain BBB transport functionality of antiepileptic drugs in epileptic rat by microdialysis in Leiden, with subsequent transport to Amsterdam for Positron Emission Tomography (PET) scanning for P-glycoprotein functionality.

Research at the Division of Pharmacology is embedded in many internal and external collaborations, such as with: Nuclear Medicine & PET research (VUMC),  the Department of Radiology (LUMC); the Swammerdam Institute of Life Sciences (SILS); and Brains On-Line, Groningen.
Research is financially supported by major grants (e.g. Top Institute Pharma; Pharmaceutical Companies).