Elizabeth (Liesbeth) de Lange
Professor Predictive Pharmacology
- Name
- Prof.dr. E.C.M. de Lange
- Telephone
- +31 71 527 6330
- ecmdelange@lacdr.leidenuniv.nl
- ORCID iD
- 0000-0001-8303-1117
Prof. Elizabeth de Lange has been trained as a chemist, with a specialization in Biophysical Chemistry (Groningen University, The Netherlands). She obtained her PhD in Pharmacology (Leiden Academic Center for Drug Research (LACDR), Leiden University, The Netherlands). She currently is the Principal Investigator on Predictive Pharmacology in the Division of Systems Pharmacology & Pharmacy at the LACDR. Her aim is to adequately predict human drug effects using predictive pharmacological (translational) approaches.
More information about Elizabeth (Liesbeth) de Lange
PhD Candidates
News
Research Projects at the Predictive Pharmacology Group
Curriculum Vitae
Prof. Elizabeth de Lange (PhD, PharmDhc) is staff member at the Division of Systems Pharmacology & Pharmacy of the Leiden Academic Center for Drug Research (LACDR). She has been trained as a Biophysical Chemist and had her PhD in Pharmacology on “The use of microdialysis to study drug transport across the blood-brain barrier in health and disease”.
Liesbeth’s ultimate aim is to predict human drug effects and early neurodegenerative disease stage by translational model development on the basis of preclinical and clinical data. To that end she underscores that the rate and extent of the body (biological systems) processes are condition dependent. Therefore, the mutual coherence and time dependencies of biological systems processes should be unraveled by strategic preclinical and clinical experimentation to obtain multilevel and longitudinal data combined with mathematical modelling (Mastermind Research Approach).
As the pharmacokinetics (PK) and pharmacodynamics (PD) of a drug are dependent on the interaction of the drug with the biological system, it depends on drug properties and rate and extent of biological systems processes. It is actually the understanding of the differences in the rate and extent of those processes between biological systems that forms the basis for interspecies and condition translation and prediction. Her research focusses on measurement of the PK of the drug in plasma; drug transport into and out of the target tissue; drug distribution within the target tissue; drug equilibration to the target site; and the ability of the drug to interact with the target, and (biomarkers of) the drug’s PD. These are interdependent. Particular emphasis lies on investigations on drug distribution to target tissues protected by special barriers, like the brain. A recent success has been the development of a physiologically-based multi-CNS compartment model that adequately predicts the PK of drugs in the different compartments of the mouse, rat and human CNS, only using the physico-chemical and biological properties of the drug.
As neurodegenerative diseases develop over time. For Alzheimer’s disease there is a lack of understanding on what makes the systems processes change in the onset of the disease, and how processes interact in disease progression. Especially the information on what causes the onset and early disease progression is important for developing intervening drugs before irreversible changes will dominate, to halt or even reverse the disease progression. Also here, the Mastermind Research Approach is applied, by measuring different endogenous compounds at different locations in preclinical species (including blood, Brain sites, CSF etc), at different stages in life. This will be translated to the human situation, and lay the foundation for a blood derived biomarker fingerprint, which is more patient friendly manner of a diagnose compared to a lumbar puncture for measuring in the cerebrospinal fluid (CSF), or (expensive) imaging modalities. Especially, a blood derived biomarker fingerprint of early stage AD would be of added value.
Liesbeth currently supervises the following PhD students and Postdocs:
- Mohammed Saleh- PhD student
- Berfin Gulave - PhD student
- Divakar Budda - PhD student
- Chunyuan Yin - PhD student
- Mengxu Zhang - PhD student
- Ming Sun - PhD student
Research Technician:
- Dirk-Jan van den Berg
An overview of research projects at the Predictive Pharmacology group.
- Prediction of human (CNS) target site concentrations in health and disease
- Predicting early Alzheimer’s disease stage in human
- Drug-target binding kinetics in vivo
- Spatial (3D) CNS drug distribution model
- Prediction of human gut (colon cancer) target site concentrations and PKPD relationships
- Pharmacometabolomics; prediction of system-wide multi-biomarker drug response.
Research Interests and Experience
- blood-brain barrier and blood-CSF-barrier transport
- intracerebral distribution
- role of transporters in (CNS) drug pharmacokinetics
- application of population mechanism-based PK and PKPD modeling
- development of physiologically based (PB) PKPD models
- drug target binding kinetics models
- translational approaches
- prediction of drug effects
- in vitro-in vivo correlations
- theoretical studies, simulations, modeling
- neurodegeneration – Alzheimer’s disease, Parkinson’s disease
- biomarkers (drug effects, disease)
- disease progression
- prediction of disease stage
- early disease biomarker fingerprints
- application and improvement of quantitative technologies
Key Publications:
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Saleh M.A.A.E.W. & Lange E.C.M. de (2021), Impact of CNS diseases on drug delivery to brain extracellular and intracellular target sites in human: a “WHAT-IF” Simulation Study, Pharmaceutics 13(1): 95.
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Qin T, Prins S, Groeneveld GJ, Van Westen G, de Vries HE, Wong YC, Bischoff LJM, de Lange ECM. Utility of Animal Models to Understand Human Alzheimer's Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals. Int J Mol Sci. 2020 Apr 30;21(9). pii: E3158. doi: 10.3390/ijms21093158
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Brink W.J. van den, Hartman R., Berg D.J. van den, Flik G., Gonzalez-Amoros B, Koopman N., Elassais-Schaap J., Graaf P.H. van der, Hankemeier T. & Lange E.C.M. de (2019), Blood- Based Biomarkers of Quinpirole Pharmacology: Cluster- Based PK/PD and Metabolomics to Unravel the Underlying Dynamics in Rat Plasma and Brain, CPT: Pharmacometrics & Systems Pharmacology 8(2): 107-117
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Witte W.E.A. de, Danhof M., Graaf P.H. van der & Lange E.C.M. de (2019), The implications of target saturation for the use of drug-target residence time, Nature Reviews Drug Discovery 18(1): 82-84
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Yamamoto Y., Välitalo P.A., Wong Y.C., Huntjens D.R., Proost J.H., Vermeulen A., Krauwinkel W., Beukers M.W., Kokki H., Kokki M., Danhof M., van Hasselt J.G.C., de Lange E.C.M., Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach. Eur J Pharm Sci. 2018; 112: 168-179.
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Vlot A.H.C., Witte W.E.A., Danhof M., van der Graaf P.H., van Westen G.J.P., de Lange E.C.M., Target and tissue selectivity prediction by integrated mechanistic pharmacokinetic-target binding and quantitative structure activity modelling AAPSJ. 2017; 20(1): 11.
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De Lange E.C.M., van der Brink W., Yamamoto Y., de Witte W., Wong Y.C., Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics. Expert Opin Drug Discov. 2017;12(12): 1207-1218.
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Brink W.J. van den, Elassais-Schaap J., Gonzalez B., Harms A., van der Graaf P.H., Hankemeier T., de Lange E.C.M., Remoxipride causes multiple pharmacokinetic/pharmacodynamic response patterns in pharmacometabolomics in rats. Eur J Pharm Sci. 2017;109: 431-440.
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De Witte W., Danhof M., van der Graaf P.H., de Lange E.C., In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant. Trends Pharmacol Sci. 2016; 37(10): 831-42.
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Stevens J., Ploeger B., Hammarlund-Udenaes M., Osswald G., van der Graaf P.H., Danhof M., de Lange E.C.M., Mechanism-based PK-PD model for the prolactin biological system response following an acute dopamine inhibition challenge: quantitative extrapolation to humans. J Pharmacokinet Pharmacodyn 2012 39(5): 463-77.
Professor Predictive Pharmacology
- Science
- Leiden Academic Centre for Drug Research
- LACDR/Pharmacology
- Budda D., Gülave B., Hasselt J.G.C. van & Lange E.C.M. de (2024), Non‐linear blood–brain barrier transport and dosing strategies influence receptor occupancy ratios of morphine and its metabolites in pain matrix, British Journal of Pharmacology : .
- Sun M.,Manson M.L., Guo T. & Lange E.C.M. de (2024), CNS viral infections—what to consider for improving drug treatment: a plea for using mathematical modeling approaches, CNS Drugs 38(5): 349-373.
- Gülave B., Budda D., Saleh M.A.A.E.W., Hasselt J.G.C. van & Lange E.C.M. de (2024), Corrigendum to “Does nonlinear blood-brain barrier transport matter for (lower) morphine dosing strategies?” , European Journal of Pharmaceutical Sciences 196: 106736.
- Zhang M., Rottschäfer V. & Lange E.C.M. de (2024), The potential impact of CYP and UGT drug-metabolizing enzymes on brain target site drug exposure, Drug Metabolism Reviews 56(1): 1-30.
- Babaei M., Evers T.M.J., Shokri F., Altucci L., Lange E.C.M. de & Mashaghi Tabari A. (2023), Biochemical reaction network topology defines dose-dependent drug-drug interactions, Computers in Biology and Medicine 155: 106584.
- Saleh M.A.A.E.W., Gülave B., Campagne O., Stewart C.F., Elassaiss J. & Lange E.C.M. de (2023), Using the LeiCNS-PK3.0 physiologically-based pharmacokinetic model to predict brain extracellular fluid pharmacokinetics in mice, Pharmaceutical Research 40: 2555-2566.
- Gülave B., Budda D., Saleh M.A.A.E.W., Hasselt J.G.C. van & Lange E.C.M. de (2023), Does nonlinear blood-brain barrier transport matter for (lower) morphine dosing strategies?, European Journal of Pharmaceutical Sciences 187: 106482.
- Faucher Q., Made T.K. van der, Lange E.C.M. de & Masereeuw R. (2023), Blood-brain barrier perturbations by uremic toxins: key contributors in chronic kidney disease-induced neurological disorders?, European Journal of Pharmaceutical Sciences 187: 106462.
- Yin C., Harms A.C., Hankemeier T., Kindt A.S.D. & Lange E.C.M. de (2023), Status of metabolomic measurement for insights in Alzheimer’s disease progression—what is missing?, International Journal of Molecular Sciences 24(5): 4960.
- Hirasawa M., Saleh M.A.A.E.W. & Lange E.C.M. de (2022), The extension of the LeiCNS-PK3.0 model in combination with the “handshake” approach to understand brain tumor pathophysiology, Pharmaceutical Research : .
- Puris E., Auriola S., Petralla S., Hartman R., Gynther M., Lange E.C.M. de & Fricker G. (2022), Altered protein expression of membrane transporters in isolated cerebral microvessels and brain cortex of a rat Alzheimer's disease model, Neurobiology of Disease 169: 105741.
- Saleh M.A.A.E.W., Bloemberg J.S., Elassaiss-Schaap J. & Lange E.C.M. de (2022), Drug distribution in brain and cerebrospinal fluids in relation to IC50 values in aging and Alzheimer's disease, using the physiologically based LeiCNS-PK3.0 model, Pharmaceutical Research 39(7): 1303-1319.
- Loryan I., Smith D.E., Artursson P., Breimer D.D., Deguchi Y., Paalzow L., Sugiyama Y., Terasaki T. & Lange E.C.M. de (2022), Professor Margareta Hammarlund-Udenaes: humbled scientist shaping modern neuropharmacokinetics, Pharmaceutical Research 39(7): 1283-1289.
- Lange E.C.M. de & Hammarlund-Udenaes M. (2022), Understanding the blood-brain barrier and beyond: challenges and opportunities for Novel CNS therapeutics, Clinical Pharmacology & Therapeutics 111(4): 758-773.
- Kok F.K., Leerdam S.L. van & Lange E.C.M. de (2022), Potential mechanisms underlying resistance to dementia in non-demented individuals with Alzheimer’s disease neuropathology, Journal of Alzheimer's Disease 87(1): 51-81.
- Hirasawa M. & Lange E.C.M. de (2022), Revisiting cerebrospinal fluid flow direction and rate in physiologically based pharmacokinetic model, Pharmaceutics 14(9): 1764.
- Saleh M.A.A.E.W., Hirasawa M., Sun M., Berfin G., Elassaiss J. & Lange E.C.M. de (2022), The PBPK LeiCNS-PK3.0 framework predicts Nirmatrelvir (but not Remdesivir or Molnupiravir) to achieve effective concentrations against SARS-CoV-2 in human brain cells, European Journal of Pharmaceutical Sciences 181: 106345.
- Saleh M.A.A.E.W. & Lange E.C.M. de (2021), Impact of CNS diseases on drug delivery to brain extracellular and intracellular target sites in human: a “WHAT-IF” Simulation Study, Pharmaceutics 13(1): 95.
- Oostveen W.M. van Lange E.C.M. de (2021), Imaging techniques in Alzheimer's disease: a review of applications in early diagnosis and longitudinal monitoring, International Journal of Molecular Sciences 22(4): 2110.
- Saleh M.A.A.E.W., Loo C.F., Elassaiss-Schaap J. & Lange E.C.M. de (2021), Lumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations, Journal of Pharmacokinetics and Pharmacodynamics 48: 725-741.
- Juhairiyah F. & Lange E.C.M. de (2021), Understanding drug delivery to the brain using liposome-based strategies: studies that provide mechanistic insights are essential, AAPS Journal 23: 114.
- Qin T., Prins S., Groeneveld J.G., Westen G.J.P. van, Vries E.H. de, Wong C.Y., Bischoff L.J.M. & Lange E.C.M. de (2020), Utility of Animal Models to Understand Human Alzheimer’s Disease, Using the Mastermind Research Approach to Avoid Unnecessary Further Sacrifices of Animals, International Journal of Molecular Sciences 21(9): 3158.
- Lebedev A.V., Nilsson J., Lindström J., Fredborg W., Akenine U., Hillilä C., Andersen P., Spulber G., Lange E.C.M. de, Berg D. van den, Kivipelto M. & Lövdén M. (2020), Effects of daily L-dopa administration on learning and brain structure in older adults undergoing cognitive training: a randomised clinical trial, Scientific Reports 10(1): 5227.
- Vendel E., Rottschäfer V. & Lange E.C.M. de (2020), A 3D brain unit model to further improve prediction of local drug distribution within the brain, PLoS ONE 15(9): e0238397.
- Vendel E., Rottschäfer V. & Lange E.C.M. de (2020), The 3D brain unit network model to study spatial brain drug exposure under healthy and pathological conditions, Pharmaceutical Research 37(7): 137.
- Hu Y., Gaillard P.J., Lange E.C.M. de & Hammarlund-Udenaes M. (2019), Targeted brain delivery of methotrexate by glutathione PEGylated liposomes: How can the formulation make a difference?, European Journal of Pharmaceutics and Biopharmaceutics 139: 197-204.
- Nicolas J.M. & Lange E.C.M. de (2019), Mind the Gaps: Ontogeny of Human Brain P-gp and Its Impact on Drug Toxicity, AAPS Journal 21: 67.
- Puris E., Gynther M., Lange E.C.M. de, Auriola S., Hammarlund-Udenaes M., Huttunen K.M. & Loryan I. (2019), Mechanistic Study on the Use of the l-Type Amino Acid Transporter 1 for Brain Intracellular Delivery of Ketoprofen via Prodrug: A Novel Approach Supporting the Development of Prodrugs for Intracellular Targets, Molecular Pharmaceutics 16(7): 3261-3274.
- Vendel E., Rottschäfer V. & Lange E.C.M. de (2019), The need for mathematical modelling of spatial drug distribution within the brain, Fluids and Barriers of the CNS 16: 12.
- Qile M., Beekman H.D.M., Sprenkeler D.J., Houtman M.J.C., Ham W.B. van, Stary-Weinzinger A., Beyl S., Hering S., Berg D.J. van den, Lange E.C.M. de, Heitman L.H., IJzerman A.P., Vos M.A. & Heyden M.A.G. van der (2019), LUF7244, an allosteric modulator/activator of Kv11.1 channels, counteracts dofetilide‐induced torsades de pointes arrhythmia in the chronic atrioventricular block dog model, British Journal of Pharmacology 176(19): 3871-3885.
- Lange E.C.M. de & Bonate P. (2019), Modeling and simulation in the translational pharmacology of CNS Drugs. In: Nomikos G.G. & Feltner D.E. (Eds.), Handbook of Behavioral Neuroscience no. 29: Elsevier. 25-37.
- Ketharanathan N., Yamamoto Y., Rohlwink U.K., Wildschut E.D., Mathôt R.A.A., Lange E.C.M. de, Wildt S.N. de, Argent A.C., Tibboel D. & Figaji A.A. (2019), Combining Brain Microdialysis and Translational Pharmacokinetic Modeling to Predict Drug Concentrations in Pediatric Severe Traumatic Brain Injury: The Next Step Toward Evidence-Based Pharmacotherapy?, Journal of Neurotrauma 36(1): 111-117.
- Vendel E., Rottschäfer V. & Lange E.C.M. de (2019), Improving the Prediction of Local Drug Distribution Profiles in the Brain with a New 2D Mathematical Model, Bulletin of Mathematical Biology 81(9): 3477-3507.
- Witte W.E.A. de, Danhof M., Graaf P.H. van der & Lange E.C.M. de (2019), The implications of target saturation for the use of drug-target residence time, Nature Reviews Drug Discovery 18(1): 82-84.
- Brink W.J. van den, Hartman R.J., Berg D.J. van den, Flik G., Gonzalez-Amoros B., Koopman N., Elassais-Schaap J., Graaf P.H. van der, Hankemeier T. & Lange E.C.M. de (2019), Blood-Based Biomarkers of Quinpirole Pharmacology: Cluster-Based PK/PD and Metabolomics to Unravel the Underlying Dynamics in Rat Plasma and Brain, CPT: Pharmacometrics and Systems Pharmacology 8(2): 107-117.
- Wong Y.C., Centanni M. & Lange E.C.M. de (2019), Physiologically Based Modeling Approach to Predict Dopamine D2 Receptor Occupancy of Antipsychotics in Brain: Translation From Rat to Human, The Journal of Clinical Pharmacology 59(5): 731-747.
- Wong Y.C., Ilkova T.I., Wijk R.C. van, Hartman R.J. & Lange E.C.M. de (2018), Development of a population pharmacokinetic model to predict brain distribution and dopamine D2 receptor occupancy of raclopride in nonanesthetized rat, European Journal of Pharmaceutical Sciences 111: 514–525.
- Witte W.E.A. de, Rottschäfer V., Danhof M., Graaf P.H. van der, Peletier L.A. & Lange E.C.M. de (2018), Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models, Journal of Pharmacokinetics and Pharmacodynamics 45(4): 621-635.
- Hurtado M.O., Kohler I. & Lange E.C.M. de (2018), Next-generation biomarker discovery in Alzheimer's disease using metabolomics - from animal to human studies, Bioanalysis 10(18): 1525-1546.
- Lange E.C.M. de, Berg D.J. van den, Bellanti F., Voskuyl R.A. & Syvänen S. (2018), P-glycoprotein protein expression versus functionality at the blood-brain barrier using immunohistochemistry, microdialysis and mathematical modeling, European Journal of Pharmaceutical Sciences 124: 61-70.
- Brink W.J. van den, Hankemeier T., Graaf P.H. van der & Lange E.C.M. de (2018), Bundling arrows: improving translational CNS drug development by integrated PK/PD-metabolomics, Expert Opinion on Drug Discovery 13(6): 539-550.
- Brink W.J. van den, Berg D.J. van den, Bonsel F.E.M., Hartman R.J., Wong Y.C., Graaf P.H. van der & Lange E.C.M. de (2018), Fingerprints of CNS drug effects: a plasma neuroendocrine reflection of D2 receptor activation using multi-biomarker pharmacokinetic/pharmacodynamic modelling, British Journal of Pharmacology 175(19): 3832-3843.
- Witte W.E.A. de, Rottschäfer V., Danhof M., Graaf P.H. van der, Peletier L.A. & Lange E.C.M. de (2018), Correction to: Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models, Journal of Pharmacokinetics and Pharmacodynamics 45(5): 763.
- Hu Y., Gaillard P.J., Rip J., Lange E.C.M. de & Hammarlund-Udenaes M. (2018), In Vivo Quantitative Understanding of PEGylated Liposome's Influence on Brain Delivery of Diphenhydramine, Molecular Pharmaceutics 15(12): 5493-5500.
- Wite W.E.A. de, Versfelt J.W., Kuzikov M., Rolland S., Georgi V., Gribbon P., Gul S., Huntjens D., Graaf P.H. van der, Danhof M., Fernández-Montalván A., Witt G. & Lange E.C.M. de (2018), In vitro and in silico analysis of the effects of D2 receptor antagonist target binding kinetics on the cellular response to fluctuating dopamine concentrations, British Journal of Pharmacology 175(21): 4121-4136.
- Brink W.J. van den, Palic S., Kohler I. & Lange E.C.M. de (2018), Access to the CNS: Biomarker Strategies for Dopaminergic Treatments, Pharmaceutical Research 35: 64.
- Brink W.J. van den, Palic S., Kohler I. & Lange E.C.M. de (2018), Correction to: Access to the CNS: Biomarker Strategies for DopaminergicTreatments, Pharmaceutical Research 35(5): 102.
- Yamamoto Y., Välitalo P.A., Wong Y.C., Huntjens D.R., Proost J.H., Vermeulen A., Krauwinkel W., Beukers M.W., Kokki H., Kokki M., Danhof M., Hasselt J.G.C. van & Lange E.C.M. de (2018), Prediction of human CNS pharmacokinetics using a physiologically-based pharmacokinetic modeling approach, European Journal of Pharmaceutical Sciences 112: 168-179.
- Verbeek J., Eriksson J., Syvänen S., Huisman M., Schuit R.C., Molthoff C.F.M., Voskuyl R.A., Lange E.C.M. de, Lammertsma A.A. & Windhorst A.D. (2018), Synthesis and preliminary preclinical evaluation of fluorine-18 labelled isatin-4-(4-methoxyphenyl)-3-thiosemicarbazone ([18F]4FIMPTC) as a novel PET tracer of P-glycoprotein expression, EJNMMI Radiopharmacy and Chemistry 3: 11.
- Erdo F., Denes L. & Lange E.C.M. de (2017), Age-associated physiological and pathological changes at the blood-brain barrier: A review, Journal of Cerebral Blood Flow and Metabolism 37(1): 4-24.
- Yamamoto Y., Välitalo P.A., Berg D.J. van den, Hartman R.J., Brink W. van den, Wong Y.C., Huntjens D.R., Proost J.H., Vermeulen A., Krauwinkel W., Bakshi S.D., Aranzana-Climent V., Marchand S., Dahyot-Fizelier C., Couet W., Danhof M., Hasselt J.G.C. van & Lange E.C.M. de (2017), A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations, Pharmaceutical Research 34(2): 333–351.
- Brink W.J. van den, Wong Y.C., Gülave B., Graaf P.H. van der & Lange E.C.M. de (2017), Revealing the Neuroendocrine Response After Remoxipride Treatment Using Multi-Biomarker Discovery and Quantifying It by PK/PD Modeling, AAPS Journal 19(1): 274–285.
- Shimizu S., Hoedt S.M. den, Mangas-Sanjuan V., Cristea S., Geuer J.K., Berg D.-J. van den, Hartman R., Bellanti F. & Lange E.C.M. de (2017), Target-Site Investigation for the Plasma Prolactin Response: Mechanism-Based Pharmacokinetic-Pharmacodynamic Analysis of Risperidone and Paliperidone in the Rat, Drug Metabolism and Disposition 45(2): 152-159.
- Bot I., Ortiz Zacarias N.V., Witte W.E. de, Vries H. de, Santbrink P.J. van, Velden D. van der, Kroener M.J., Berg D.J. van den, Stamos D., Lange E.C.M. de, Kuiper J., IJzerman A.P. & Heitman L.H. (2017), A novel CCR2 antagonist inhibits atherogenesis in apoE deficient mice by achieving high receptor occupancy, Scientific Reports 2017(7): 52.
- Schuetz D.A., Witte W.E.A. de, Wong Y.C, Knasmueller B., Richter L., Kokh D.B., Sadiq S.K., Bosma R., Nederpelt I., Heitman L.H., Segala E., Amaral M., Guo D., Andres D., Georgi V., Stoddart L.A., Hill S., Cooke R.M., Graaf C. de, Leurs R., Frech M., Wade R.C., Lange E.C.M. de, IJzerman A.P., Mueller-Fahrnow A. & Ecker G.F. (2017), Kinetics for Drug Discovery: an industry-driven effort to target drug residence time, Drug Discovery Today 22(6): 896-911.
- Yamamoto Y., Danhof M. & Lange E.C.M. de (2017), Microdialysis: the key to physiologically based model prediction of human CNS target site concentrations, AAPS Journal 19(4): 891-909.
- Hu Y., Rip J., Gaillard P.J., Lange E.C.M. de & Hammarlund-Udenaes M. (2017), The impacts of liposomal formulations based on different phospholipids on the in vivo release and brain delivery of methotrexate: a microdialysis study, European Journal of Pharmaceutical Sciences 106(9): 2606-2613.
- Kervezee L., Berg D.J. van den, Hartman R.J., Meijer J.H. & Lange E.C.M. de (2017), Diurnal variation in the pharmacokinetics and brain distribution of morphine and its major metabolite, European Journal of Pharmaceutical Sciences 109: S122-S130.
- Witte W.E.A. de, Vauquelin G., Graaf P.H. van der & Lange E.C.M. de (2017), The influence of drug distribution and drug-target binding on target occupancy: The rate-limiting step approximation, European Journal of Pharmaceutical Sciences 109S: S83-S89.
- Dijkman S.C. van, Voskuyl R.A. & Lange E.C.M. de (2017), Biomarkers in epilepsy - a modelling perspective, European Journal of Pharmaceutical Sciences 109: S47-S52.
- Lange E.C.M. de, Bajza A., Imre P., Csorba A., Denes L. & Erdo F. (2017), Age-associated changes at the blood-brain barrier. In: Shamim A. (Ed.), Aging: exploring a complex phenomenon: Taylor & Francis/CRC Press.
- Yamamoto Y., Valitalo P.A.J., Huntjens D.R., Proost J.H., Vermeulen A., Krauwinkel W., Beukers M.W., Berg D.J. van den, Hartman R.J., Wong Y.C., Danhof M., Hasselt J.G.C. van & Lange E.C.M. de (2017), Predicting Drug Concentration-Time Profiles in Multiple CNS Compartments Using a Comprehensive Physiologically-Based Pharmacokinetic Model, CPT: Pharmacometrics and Systems Pharmacology 6(11): 765–777.
- Burggraaf J., Breimer D.D., Graaf P.H. van der. & Lange E.C.M. de (2017), Editorial Special Supplement of the European Journal of Pharmaceutical Sciences on the occasion of the retirement of Professor Meindert Danhof as Professor of Pharmacology at Leiden University, European Journal of Pharmaceutical Sciences 109(Supplement): S1.
- Ketharanathan N., Yamamoto Y., Rohlwink U., Wildschut E.D., Hunfeld M., Lange E.C.M. de & Tibboel D. (2017), Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities, Child's Nervous System 33(10): 1703-1710.
- Nederpelt I., Kuzikov M., Witte W.E.A. de, Schnider P., Tuijt B., Gul S., IJzerman A.P., Lange E.C.M. de & Heitman L.H. (2017), From receptor binding kinetics to signal transduction; a missing link in predicting in vivo drug-action, Scientific Reports 7: 14169.
- Yamamoto Y., Danhof M. & Lange E.C.M. de (2017), Erratum to: Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations, AAPS Journal 19(4): 1249-1252.
- Taneja A., Vermeulen A., Huntjens D.R.H., Danhof M., Lange E.C.M. de & Proost J.H. (2017), Modeling of prolactin response following dopamine D-2 receptor antagonists in rats: can it be translated to clinical dosing?, Pharmacology Research and Perspectives 5(6): e00364.
- Brink W.J. van den, Elassaiss J., Gonzalez Amoros B., Harms A.C., Graaf P.H. van der, Hankemeier T. & Lange E.C.M. de (2017), Multivariate pharmacokinetic/pharmacodynamic (PKPD) analysis with metabolomics shows multiple effects of remoxipride in rats, European Journal of Pharmaceutical Sciences 109: 431-440.
- Lange E.C.M. de., Brink W.J. van den, Yamamoto Y., Witte W.E.A. de & Wong Y.C. (2017), Novel CNS drug discovery and development approach: model-based integration to predict neuro-pharmacokinetics and pharmacodynamics, Expert Opinion on Drug Discovery 12(12): 1207-1218.
- Chen X., Slattengren T., Lange E.C.M. de, Smith D.E. & Hammarlund-Udenaes M. (2017), Revisiting atenolol as a low passive permeability marker, Fluids and Barriers of the CNS 14: 30.
- Hu Y., Rip J., Gaillard P.J., Lange E.C.M. de. & Hammarlund-Udenaes M. (2017), The Impact of Liposomal Formulations on the Release and Brain Delivery of Methotrexate: An In Vivo Microdialysis Study, Journal of Pharmaceutical Sciences 106(9): 2606-2613.
- Vlot A.H.C., Witte W.E.A. de, Danhof M., Graaf P.H. van der, Westen G.J.P. van & Lange E.C.M. de (2017), Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling, AAPS Journal 20(1): 11.
- Taneja A., Vermeulen A., Huntjens D.R.H., Danhof M., Lange E.C.M. de & Proost J.H. (2016), A comparison of two semi-mechanistic models for prolactin release and prediction of receptor occupancy following administration of dopamine D-2 receptor antagonists in rats, European Journal of Pharmacology 789: 202-214.
- Yamamoto Y., Ketharanathan N., Lange E.C.M. de, Rohlwink U., Wildschut E.D., Mathot R.A.A., Tibboel D. & Figaji A.A. (2016), Prediction of cerebral morphine concentration in pediatric traumatic brain injury (tbi) with the rat physiologically based pharmacokinetic (pbpk) model, Journal of Neurotrauma 33(3): A38-A38.
- Witte W.E., Wong Y.C., Nederpelt I., Heitman L.H., Danhof M., Graaf P.H. van der, Gilissen R.A. & De Lange E.C. (2016), Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients, Expert Opinion on Drug Discovery 11(1): 45-63.
- Bakshi S.D., Lange E.C.M. de, Graaf P.H. van der, Danhof M. & Peletier L.A. (2016), Understanding the Behavior of Systems Pharmacology Models Using Mathematical Analysis of Differential Equations: Prolactin Modeling as a Case Study, CPT: Pharmacometrics and Systems Pharmacology 5(7): 339-351.
- Witte W.E.A. de, Danhof M., Graaf P.H. van der & Lange E.C.M. de (2016), In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant, Trends in Pharmacological Sciences 37(10): 831-842.
- Ruigrok M.J.R. & Lange E.C.M. de (2015), Emerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans, AAPS Journal 17(3): 493-505.
- Lange E.C.M. de & Hammarlund-Udenaes M. (2015), Translational aspects of blood-brain barrier transport and central nervous system effects of drugs: from discovery to patients, Clinical Pharmacology & Therapeutics 97(4): 380-394.
- Lange E.C.M. de (2015), PBPK Modeling Approach for Predictions of Human CNS Drug Brain Distribution 296. In: Di L. & Kerns E.H. (Eds.), Blood-Brain Barrier in drug discovery: optimizing brain exposure of CNS drugs and minimizing brain side effects: Wiley. 296-323.
- Westerhout J., Van den Berg D.J., Hartman R., Danhof M. & De Lange E.C. (2014), Prediction of methotrexate CNS distribution in different species - influence of disease conditions, European Journal of Pharmaceutical Sciences 2014(Jan 22): 0928-0987.
- Rip J., Chen L., Hartman R., Heuvel A. van den, Reijerkerk A., Kregten J. van, Boom B. van der, Appeldoorn C., Boer M. de, Maussang D., Lange E.C. de & Gaillard P.J. (2014), Glutathione PEGylated liposomes: pharmacokinetics and delivery of cargo across the blood-brain barrier in rats, Journal of Drug Targeting 22(3): .
- Kervezee L., Hartman R.J., Berg D.J. van den, Shimizu S., Yamamoto Y., Meijer J.H. & Lange E.C.M. de (2014), Diurnal variation in P-glycoprotein-mediated transport and cerebrospinal fluid turnover in the brain, AAPS Journal 16(5): 1029-1037.
- Lange E.C.M. de (2014), Pharmacometrics in Psychiatric Diseases. In: Schmidt S. & Derendorf H. (Eds.), Applied Pharmacometrics. AAPS Advances in the Pharmaceutical Sciences Series no. 14. New York, NY, U.S.A.: Springer. 407-449.
- Lange E.C.M. de (2014), PKPD aspects of brain drug delivery in a translational perspective. In: Hammarlund-Udenaes M., Lange E.C.M. de & Thorne R. (Eds.), Drug delivery to the brain. AAPS Advances in the Pharmaceutical Sciences Series no. 10. New York, NY, U.S.A.: Springer. 233-268.
- Lange E.C.M. de (2014), Disease influence on BBB transport in neurodegenerative disorders. In: Hammarlund-Udenaes M., Lange E.C.M. de & Thorne R. (Eds.), Drug delivery to the brain. AAPS Advances in the Pharmaceutical Sciences Series no. 10. New York, NY, U.S.A.: Springer. 591-634.
- Westerhout Joost, Smeets Jean, Danhof Meindert & De Lange Elizabeth C.M. (2013), The impact of P-gp functionality on non-steady state relationships between CSF and brain extracellular fluid, Journal of Pharmacokinetics and Pharmacodynamics 40(3): 327-342.
- De Lange Elizabeth C.M. (2013), Utility of CSF in translational neuroscience, Journal of Pharmacokinetics and Pharmacodynamics 40(3): 315-326.
- Syvanen Stina, Russmann Vera, Verbeek Joost, Eriksson Jonas, Labots Maaike, Zellinger Christina, Seeger Natalie, Schuit Robert, Rongen Marissa, Van Kooij Rolph, Windhorst A.D., Lammertsma A.A., De Lange E.C., Voskuyl R.A., Koepp Matthias & Potschka Heidrun (2013), [C-11]quinidine and [C-11]laniquidar PET imaging in a chronic rodent epilepsy model: Impact of epilepsy and drug-responsiveness, NUCLEAR MEDICINE AND BIOLOGY 40(6): 764-775.
- Stevens J., Ploeger B.A., Hammarlund-Udenaes M., Osswald G., Graaf P.H. van der, Danhof M. & Lange E.C.M. de (2012), Mechanism-based PK-PD model for the prolactin biological system response following an acute dopamine inhibition challenge: quantitative extrapolation to humans, Journal of Pharmacokinetics and Pharmacodynamics 39(5): 463-477.
- Verbeek J., Syvanen S., Schuit R.C., Eriksson J., Lange E.C.de, Windhorst A.D., Luurtsema G. & Lammertsma A.A. (2012), Synthesis and preclinical evaluation of [C-11]D617, a metabolite of (R)-[C-11]verapamil, NUCLEAR MEDICINE AND BIOLOGY 39(4): 530-539.
- Lange E.C.M. de (2012), The Physiological Characteristics and Transcytosis Mechanisms of the Blood-Brain Barrier (BBB), Current pharmaceutical biotechnology 13(12): 2319-2327.
- Taneja A., Nyberg J., Lange E.C. de, Danhof M. & Della Pasqua O.E. (2012), Application of ED-optimality to screening experiments for analgesic compounds in an experimental model of neuropathic pain, Journal of Pharmacokinetics and Pharmacodynamics 39(6): 673-681.
- Syvanen S., Labots M., Tagawa Y., Eriksson J., Windhorst A.D., Lammertsma A.A., Lange E.C.M. de & Voskuyl R.A. (2012), Altered GABA(A) Receptor Density and Unaltered Blood Brain Barrier Transport in a Kainate Model of Epilepsy: An In Vivo Study Using C-11-Flumazenil and PET, Journal of Nuclear Medicine 53(12): 1974-1983.
- Syvanen S., Schenke M., Berg D.J. van den, Voskuyl R.A. & Lange E.C.M. de (2012), Alteration in P-glycoprotein Functionality Affects Intrabrain Distribution of Quinidine More Than Brain Entry-A Study in Rats Subjected to Status Epilepticus by Kainate, AAPS Journal 14(1): 87-96.
- Westerhout J., Ploeger B., Smeets J., Danhof M. & Lange E.C.M. de (2012), Physiologically Based Pharmacokinetic Modeling to Investigate Regional Brain Distribution Kinetics in Rats, AAPS Journal 14(3): 543-553.
- Lange E.C.M. de (2012), Recovery and calibration techniques: toward quantitative microdialysis. In: Mueller M. (Ed.), Microdialysis in drug development. AAPS Advances in the Pharmaceutical Sciences Series no. 4. New York, NY, U.S.A.: Springer. 13-33.
- Westerhout J., Danhof M. & De Lange E.C. (2011), Preclinical prediction of human brain target site concentrations: considerations in extrapolating to the clinical setting, JOURNAL OF PHARMACEUTICAL SCIENCES 100(9): .
- Syvanen S., De Lange E.C., Tagawa Y., Schenke M., Molthoff C.F., Windhorst A.D., Lammertsma A.A. & Voskuyl R.A. (2011), Simultaneous in vivo measurements of receptor density and affinity using [11C]flumazenil and positron emission tomography: comparison of full saturation and steady state methods, NEUROIMAGE 57(3): .
- Stevens J., Ploeger B.A., Van der Graaf P.H., Danhof M. & De Lange E.C. (2011), Systemic and Direct Nose-to-Brain Transport Pharmacokinetic Model for Remoxipride after Intravenous and Intranasal Administration, Drug Metabolism and Disposition 39(12): .
- Steeg T.J. van, Krekels E.H.J., Freijer J., Danhof M. & Lange E.C.M. de (2010), Effect of altered AGP plasma binding on heart rate changes by S(-)-propranolol in rats using mechanism-based estimations of in vivo receptor affinity (K(B,vivo)), JOURNAL OF PHARMACEUTICAL SCIENCES 99(5): 2511-2520.
- Stevens J., Van den Berg D.J., De Ridder S., Niederlander H.A., Van der Graaf P.H., Danhof M. & De Lange E.C. (2010), Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 878(13-14): .
- Kooij G., Horssen J. van, Lange E.C.M. de, Reijerkerk A., Pol S.M.A. van der, Hof B. van het, Drexhage J., Vennegoor A., Killestein J., Scheffer G., Oerlemans R., Scheper R., Valk P. van der, Dijkstra C.D. & Vries H.E. de (2010), T lymphocytes impair P-glycoprotein function during neuroinflammation, Journal of Autoimmunity 34(4): 416-425.
- Van Steeg T.J., Krekels E.H., Freijer J., Danhof M. & De Lange E.C. (2010), Effect of altered AGP plasma binding on heart rate changes by S(-)-propranolol in rats using mechanism-based estimations of in vivo receptor affinity (K(B,vivo)), JOURNAL OF PHARMACEUTICAL SCIENCES 99(5): .
- Stevens J., Berg D.J. van den, Ridder S. de, Niederländer H.A., Graaf P.H. van der, Danhof M. & Lange E.C.M. de (2010), Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 878(13-14): 969-975.
- Steeg T.J. van, Boralli V.B., Krekels E.H.J., Slijkerman P., Freijer J., Danhof M. & Lange E.C.M. de (2009), Influence of plasma protein binding on pharmacodynamics: Estimation of in vivo receptor affinities of beta blockers using a new mechanism-based PK-PD modelling approach, JOURNAL OF PHARMACEUTICAL SCIENCES 98(10): 3816-28.
- Stevens J., Suidgeest E., Van der Graaf P.H., Danhof M. & De Lange E.C. (2009), A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs, Pharmaceutical Research 26(8): 1911-7.
- Cremers T.I.F.H., Vries M.G. de, Huinink K.D., Loon J.P. van, Hart M. van der, Ebert B., Westerink B.H.C. & Lange E.C.M. de (2009), Quantitative microdialysis using modified ultraslow microdialysis: Direct rapid and reliable determination of free brain concentrations with the MetaQuant technique, Journal of Neuroscience Methods 178(2): 249-254.
- Voskuyl R.A., Syvanen S., Luurtsema G., Molthoff C.F., Windhorst A.D., Huisman M.C., Lammertsma A.A. & Lange E.C.M. de. (2009), On the role of P-glycoprotein function in the blood-brain barrier in pharmacoresistance: A pet study in epileptic rats, Epilepsia 50(11): 337-337.
- Stevens J., Hammarlund-Udenacs M., Graaf P.H. van der, Danhof M. & Lange E.C.M. de (2009), Remoxipride in man and rat: A population-Approach pharmacokinetic model, The Journal of Clinical Pharmacology 49(9): 1099-1099.
- Danhof M., Lange E.C.M. de, Della Pasqua O.E., Ploeger B.A. & Voskuyl R.A. (2008), Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research, Trends in Pharmacological Sciences 29(4): 186-191.
- Ravenstijn P.G.M., Merlini M., Hameetman M., Murray T.K., Ward M.A., Lewis H., Ball G., Mottart C., Ville de Goyet C. de, Lemarchand T., Belle K. van, O'Neill M.J., Danhof M. & Lange E.C.M. de (2008), The exploration of rotenone as a toxin for inducing Parkinson's disease in rats, for application in BBB transport and PK-PD experiments, Journal of Pharmacological and Toxicological Methods 57(2): 114-130.
- Groenendaal D., Frijer J., Rosier A., Mik D. de, Nichols G., Hersey A., Ayrton A.D., Danhof M. & Lange E.C. de (2008), Pharmacokinetic/pharmacodynamic modelling of the EEG effects of opioids: the role of complex biophase distribution kinetics, European Journal of Pharmaceutical Sciences 34(2-3): 149-163.
- Steeg T.J. van, Freijer J.L., Danhof M. & Lange E.C.M. de (2008), Mechanism-based pharmacodynamic modeling of S(-)-Atenolol: Estimation of in vivo affinity for the beta1-adrenoceptor with an agonist-antagonist interaction model, Journal of Pharmacology and Experimental Therapeutics 324(3): 1234-1342.
- Steeg T.J. van, Krekels E.H., Danhof M. & Lange E.C.M. de (2007), Reproducible and time-dependent modification of serum protein binding in Wistar Kyoto rats, Journal of Pharmacological and Toxicological Methods 56(1): 72-78.
- Groenendaal D., Freijer J.L., Mik D. de, Bouw M.R., Danhof M. & Lange E.C.M. de (2007), Influence of biophase distribution and P-glycoprotein interaction on pharmacokinetic-pharmacodynamic modelling of the effects of morphine on the EEG, British Journal of Pharmacology 151(5): 713-720.
- Groenendaal D., Freijer J.L., Mik D. de, Bouw M.R., Danhof M. & Lange E.C.M. de (2007), Population pharmacokinetic modelling of non-linear brain distribution of morphine: influence of active saturable influx and P-glycoprotein mediated efflux, British Journal of Pharmacology 151(5): 701-712.
- Steeg T.J. van, Krekels E.H.J., Danhof M. & Lange E.C.M. de (2007), Reproducible and time-dependent modification of serum protein binding in Wistar Kyoto rats, Journal of Pharmacological and Toxicological Methods 56(1): 72-78.
- Lange E.C.M. de (2007), Microdialysis as a method to study the blood-brain barrier. In: Cremers T.H.I.F. & Westerink B.H.C. (Eds.), Handbook of Microdialysis: Methods, Applications and Perspectives: Academic Press. 545-572.
- Lange E.C.M. de (2007), Multidrug resistance P-glycoprotein and other transporters. In: Fink G. (Ed.), Encyclopedia of Stress: Academic Press. 774-783.
- Steeg T.J. van, Freijer J.L., Danhof M. & Lange E.C.M. de (2007), Pharmacokinetic-pharmacodynamic modelling of S(-)-atenolol in rats: reduction of isoprenaline-induced tachycardia as a continuous pharmacodynamic endpoint, British Journal of Pharmacology 151(3): 356-366.
- Danhof M., Jongh J. de, Lange J., Della Pasqua O.E., Ploeger B.A. & Voskuyl R.A. (2007), Mechanism-Based Pharmacokinetic-Pharmacodynamic Modeling: Biophase Distribution, Receptor Theory, and Dynamical Systems Analysis, Annual Review of Pharmacology and Toxicology 47: 357-400.
- Lange E.C.M. de (2006), Microdialysis as a method to study Blood-Brain Barrier transport mechanisms. In: Cremers T.I.F.H. & Westerink B.H.C. (Eds.), Handbook of Microdialysis: Methods, applications and Perspectives.
- Lange E.C.M. de (2006), Multidrug resistance P-glycoprotein and other transporters. In: , Encyclopedia of Stress II.
- Groenendaal D., Blom-Roosemalen M.C.M., Danhof M. & Lange E.C.M. de (2005), High-performance liquid chromatography of nalbuphine, butorphanol and morphine in blood and brain microdialysate samples: application to pharmacokinetic/pharmacodynamic studies in rats, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences 822(1-2): 230-237.
- Lange E.C.M. de, Ravenstijn P.G.M., Groenendaal D. & Steeg T.J. van (2005), Related Articles, Toward the prediction of CNS drug-effect profiles in physiological and pathological conditions using microdialysis and mechanism-based pharmacokinetic-pharmacodynamic modeling, The AAPS Journal 7(3): E532-543.
- Lange E.C.M. de (2004), Potential role of ABC transporters as a detoxification system at the blood-CSF barrier, Advanced Drug Delivery Reviews 14: 1793-1809.
- Lange E.C.M. de (2003), De bloedhersen-barrière en het transport van geneesmiddelen, Tijdschrift voor Neurologie en Neurochirurgie 104(4): 235-240.
- Lange E.C.M. de & Danhof M. (2002), Considerations in the Use of Cerebrospinal Fluid Pharmacokinetics to Predict Brain Target Concentrations in the Clinical Setting; Implications of the Barriers between Blood and Brain, Clinical Pharmacokinetics 41: 691-703.
- Sills G.J., Kwan P., Butler E., Lange E.C.M. de, Berg D.J. van den & Brodie M.J. (2002), P-glycoprotein mediated efflux of anti-epileptic drugs: preliminary studies in mdr1a knockout mice, Epilepsy & Behavior 3: 427-432.
- Mulder M., Blokland A, Berg D.J. van den, Schulten H, Bakker A.H.F., Terwel D, Honig W., Kloet E.R. de, Havekes L.M., Steinbusch HWM & Lange E.C.M. de (2001), Apolipoprotein E protect against neuropathology induced by a high-fat diet and maintains the integrity of the blood-brain barrier during aging, Laboratory Investigation 81(7): 953-960.
- Karssen A.M., Meijer O.C., Sandt I.C.J. van der, Lucassen P.J., Lange E.C.M. de, Boer A.G. de & Kloet E.R. de (2001), Multidrug resistance P-glycoprotein hampers the access of cortisol but not of corticosterone to mouse and human brain, Endocrinology 142: 2686-2694.
- Boer A.G de, Lange E.C.M. de, Sandt I.C.J. van der & Breimer D.D. (2000), The application of microdialysis techniques to the study of drug transport across the blood-brain-barrier. In: Begley D.J., Bradbury M.W. & Kreuter J. (Eds.), The blood-brain barrier and drug delivery to the CNS: CRC Press.
- Lange E.C.M. de, Boer A.G. de & Breimer D.D. (1999), Microdialysis for pharmacokinetic analysis of drug transport to the brain, Advanced Drug Delivery Reviews 36(2,3): 211-228.
- Xie R.J., Hammarlund-Udenaes M., Boer de A.G. & Lange de E.C.M. (1999), The role of P-glycoprotein in blood-brain barrier transport of morphine: transcortical microdialysis studies in mdr1a (-/-) and mdr1a (+/+)mice, British Journal of Pharmacology 128(3): 563-568.
- Boer A.G. de, Lange E.C.M. de, Sandt I.C.J. van der & Breimer D.D. (1998), Transporters and the blood-brain barrier (BBB), International Journal of Clinical Pharmacology and Therapeutics 36(1): 14-15.
- Desrayaud S., Lange E.C.M. de, Lemaire M., Bruelisauer A., Boer A.G. de & Breimer D.D. (1998), Effect of the Mdr1a P-glycoprotein gene disruption on the tissue distribution of SDZ PSC 833, a multidrug resistance-reversing agent, in mice, Journal of Pharmacology and Experimental Therapeutics 285(2): 438-443.
- Lange E.C.M. de, Boer A.G. de & Breimer D.D. (1998), Intracerebral microdialysis. In: Pardridge W.M. (Ed.), An introduction to the blood-brain-barrier. Cambridge, USA: Cambridge University Press. 94-112.
- Meijer O.C., Lange E.C.M. de, Boer A.G. de, Workel J.O., Breimer D.D. & Kloet E.R. de (1998), Penetration of dexamethasone into brain glucocorticoid targets is enhanced in mdr1A P-glycoprotein knockout mice, Endocrinology 139: 1789-1793.
- Lange E.C.M. de, Bock G.H. de, Schinkel G., Boer A.G. de & Breimer D.D. (1998), BBB Transport and P-glycoprotein functionality using mdr1A (-/-) and Wild-type mice. Total brain versus microdialysis concentration profiles of rhodamine-123, PHARMACEUTICAL RESEARCH 15(11): 1657-1665.
- Hammarlund-Udenaes M., Paalzow L.K. & Lange E.C.M. de (1997), Drug equilibration across the blood-brain barrier - Pharmacokinetic considerations based on the microdialysis method, PHARMACEUTICAL RESEARCH 14(2): 128-134.
- Boer A.G. de, Gaillard P.J., Lange E.C.M. de, Danhof M., Vries H.E. de, Kuiper J. & Breimer D.D. (1997), Drug transport across blood-brain barriers: in vitro vs. in vivo models, Developments in animal and veterinary sciences 27: 873-879.
- Lange E.C.M. de, Boer A.G. de & Breimer D.D. (1997), Monitoring in vivo blood-brain barrier drug transport: Cerebrospinal fluid sampling, the unit impulse response method and, with special reference, intracerebral microdialysis, S.T.P. Pharma Sciences 7(1): 17-27.
- Lange E.C.M. de, Danhof M., Boer A.G. de & Breimer D.D. (1997), Methodological considerations of intracerebral microdialysis in pharmacokinetic studies on drug transport across the blood-brain barrier, Brain research reviews 25(1): 27-49.
- Lange E.C.M. de (1997), Effect of perfusate tonicity and temperature on microdialysate AUC values of acetaminophen and atenolol obtained from rat cortical brain. In: Boer A.G. de & Sutanto W. (Eds.), Drug transport across the blood-brain-barrier. In vitro and in vivo techniques. Amsterdam: Harwood Academic Publishers. 157-163.
- Lange E.C.M. de, Vries J.D. de, Zurcher C., Danhof M., Boer A.G. de & Breimer D.D. (1995), The use of intracerebral microdialysis for the determination of pharmacokinetic profiles of anticancer drugs in tumor-bearing rat brain, PHARMACEUTICAL RESEARCH 12(12): 1924-1931.
- Lange E.C.M. de, Hesselink M.B., Danhof M., Boer A.G. de & Breimer D.D. (1995), The use of intracerebral microdialysis to determine changes in blood-brain-barrier transport, PHARMACEUTICAL RESEARCH 12(1): 129-133.
- Lange E.C.M. de, Danhof M., Zurcher C., Boer A.G. de & Breimer D.D. (1995), Repeated microdialysis perfusions: periprobe tissue reactions and BBB permeability, Brain Research 702(1-2): 261-265.
- Lange E.C.M. de, Bouw M.R., Mandema J.W., Danhof M., Boer A.G. de & Breimer D.D. (1995), Application of intracerebral microdialysis to study regional distribution kinetics of drugs in rat-brain, British Journal of Pharmacology 116(5): 2538-2544.
- Boer A.G. de, Vries H.E. de, Lange E.C.M. de, Danhof M., Kuiper J. & Breimer D.D. (1994), Drug transport to the brain: in-vitro versus in-vivo approaches, JOURNAL OF CONTROLLED RELEASE 28(1-3): 259-263.
- Lange E.C.M. de, Danhof M., Boer A.G. de & Breimer D.D. (1994), Critical factors of intracerebral microdialysis as a technique to determined the pharmacokinetics of drugs in rat brain, Brain Research 666(1): 1-8.
- Lange E.C.M. de, Danhof M., Boer A.G. de & Breimer D.D. (1993), The use of intracerebral microdialysis to study blood-brain-barrier transport in health, after modification and in disease. In: Drewes L.R. & Betz A.L. (Eds.), Frontiers in Cerebral Vascular Biology. Advances in Experimental Medicine and Biology no. 331. New York: Springer. 257-262.
- Lange E.C.M. de, Danhof M., Boer A.G. de & Breimer D.D. (1991), The use of intracerebral microdialysis for the characterization of drug transport into the brain. Rollema H., Westerink B.H.C. & Drijfhout W.J. (Eds.), 5th International Conference on In Vivo Methods. Monitoring molecules in neuroscience 21 September 1991 - 24 September 1991: International Society for Monitoring Molecules in Neuroscience. 74-75.
- Geven van cursuseen (1 maal per jaar BBB cursus), geven van advies (kleine omvang, incidenteel)
- Geven van cursussen (BBB curus 1 jaarlijks), geven van advies (kleine omvang, incidenteel)
- Chair Scientific Advisory Board
- Directeur / eigenaar