Piet Hein van der Graaf
Professor Systems Pharmacology
- Name
- Prof.dr. P.H. van der Graaf
- Telephone
- +31 71 527 2727
- p.vandergraaf@lacdr.leidenuniv.nl
Piet van der Graaf was appointed as Professor of Systems Pharmacology in 2012. He is also Vice President and Head of Quantitative Systems Pharmacology (QSP) at Certara.
Between 2013-2016, he was the Director of Research of the Leiden Academic Centre for Drug Research (LACDR).
From 1999 – 2013 he held various leadership positions at Pfizer in Sandwich (United Kingdom) in Discovery Biology (Head of Sexual Health Therapeutic Area), Pharmacokinetics and Drug Metabolism (Head of Translational Quantitative Pharmacology) and Clinical Pharmacology/Pharmacometrics. He was involved in a large number of drug discovery and development programs in multiple therapeutic areas and responsible for the nomination of more than 10 clinical development candidates. He holds several patents in the field of target discovery.
Between 1990-1994 he received his doctorate training in quantitative receptor pharmacology with Nobel laureate Sir James Black at King's College London and thereafter worked as a postdoctoral fellow of the Royal Netherlands Academy of Sciences at Leiden University on the development of mechanism-based pharmacokinetic-pharmacodynamic (PKPD) approaches.
He is founding Editor-in-Chief of CPT: Pharmacometrics & Systems Pharmacology, responsible for the successful launch of this new Open Access journal.
Piet is Fellow of the British Pharmacological Society, has (co-)authored more than 100 papers and book chapters in the area of quantitative and translational pharmacology and has given more than 100 lectures at international symposia and workshops.
Piet is currently also member of the Expert Review Panel of the Singapore Biomedical Council Asset Review (A*STAR) and member of the Leo Foundation Nomination Committee.
Professor Systems Pharmacology
- Science
- Leiden Academic Centre for Drug Research
- LACDR/Pharmacology
- Mehta K.M., Guo T. & Graaf P.H. van der Hasselt J.G.C. van (2024), Model‐based dose optimization framework for bedaquiline, pretomanid, and linezolid for the treatment of drug‐resistant tuberculosis, British Journal of Clinical Pharmacology 90(2): 463-474.
- Desikan R., Germani M., Graaf P.H. van der & Magee M. (2024), A quantitative clinical pharmacology-based framework for model-informed vaccine development, Journal of Pharmaceutical Sciences 113(1): 22-32.
- Geerts H., Bergeler S., Lytton W.W. & Graaf P.H. van der (2024), Computational neurosciences and quantitative systems pharmacology: a powerful combination for supporting drug development in neurodegenerative diseases, Journal of Pharmacokinetics and Pharmacodynamics 51: 563-573.
- Mehta K.M., Balazki P., Graaf P.H. van der, Guo T. & Hasselt J.G.C. van (2024), Predictions of bedaquiline central nervous system exposure in patients with tuberculosis meningitis using physiologically based pharmacokinetic modeling, Clinical Pharmacokinetics 63: 657-668.
- Danhof M., Graaf P.H. van der, Post T.M., Visser S.A.G., Zuideveld K.P. & Schmidt S. (2024), In memoriam Lambertus (“Bert”) A. Peletier 29 March 1937–16 December 2023: furthering quantitative pharmacology through applied mathematics, CPT: Pharmacometrics & Systems Pharmacology 13(10): 1611-1614.
- Fu Y., Snelder N., Guo T., Graaf P.H. van der & Hasselt J.G.C. van (2023), Evaluation of a cardiovascular systems model for design and analysis of hemodynamic safety studies, Pharmaceutics 15(4): 1175.
- Mehta K.M., Guo T., Graaf P.H. van der & Hasselt J.G.C. van (2023), Predictions of bedaquiline and pretomanid target attainment in lung lesions of tuberculosis patients using translational minimal physiologically based pharmacokinetic modeling, Clinical Pharmacokinetics 62(3): 519-532.
- Chung D., Bakshi S. & Graaf P.H. van der (2023), A review of quantitative systems pharmacology models of the coagulation cascade: opportunities for improved usability, Pharmaceutics 15(3): 918.
- Geerts H., Walker M., Rose R., Bergeler S., Graaf P.H. van der, Schuck E., Koyama A., Yasuda S., Hussein Z., Reyderman L., Swanson C. & Cabal A. (2023), A combined physiologically‐based pharmacokinetic and quantitative systems pharmacology model for modeling amyloid aggregation in Alzheimer's disease, CPT: Pharmacometrics & Systems Pharmacology 12(4): 444-461.
- Graaf P.H. van der (2023), Mush room for improving therapeutic approaches in psychiatry, Clinical Pharmacology & Therapeutics 113(4): 757-759.
- Minichmayr I.K., Smith D.M., Giacomini K.M. & Graaf P.H. van der (2023), Trends in clinical pharmacology and therapeutics, Clinical Pharmacology & Therapeutics 114(1): 11-14.
- Geerts H., Bergeler S., Walker M., Graaf P.H. van der & Courade J.-P. (2023), Analysis of clinical failure of anti-tau and anti-synuclein antibodies in neurodegeneration using a quantitative systems pharmacology model, Scientific Reports 13(1): 14342 (14342).
- Venkatakrishnan K., Brown K.E.., Giacomini K.M. & Graaf P.H. van der (2023), Diversity, equity, and inclusion: translating clinical pharmacology for all, Clinical Pharmacology & Therapeutics 113(3): 457-461.
- Rowland G, Kronbichler A., Smith R., Jayne D., Graaf P.H. van der & Chelliah V. (2023), Using a network-based analysis approach to investigate the involvement of S. aureus in the pathogenesis of granulomatosis with polyangiitis, International Journal of Molecular Sciences 24(3): 1822.
- Choi Y., Vinks A.A. & Graaf P.H. van der (2023), Novel therapeutic modalities: the future is now, Clinical Pharmacology & Therapeutics 114(3): 493-496.
- Matthews R.J., Hollinshead D., Morrison D., Graaf P.H. van der & Kierzek A.M. (2023), QSP Designer: quantitative systems pharmacology modeling with modular biological process map notation and multiple language code generation, CPT: Pharmacometrics & Systems Pharmacology 12(7): 889-903 .
- Smith D.M., Minichmayr I.K., Standing J.F., Giacomini K.M., Graaf P.H. van der & Peck R.W. (2023), Ensuring transparency and quality of clinical trial reporting in clinical pharmacology & therapeutics: prospective trial registration and compliance with reporting guidelines are required for all clinical trials, Clinical Pharmacology & Therapeutics 114(6): 1153-1157.
- Graaf P.H. van der (2023), Clinical significance of therapeutic peptide and protein drug Interactions: a call to action, Clinical Pharmacology & Therapeutics 113(6): 1173-1174.
- Mehta K.M., Spaink H.P., Ottenhoff T.H.M., Graaf P.H. van der & Hasselt J.G.C. van (2022), Host-directed therapies for tuberculosis: quantitative systems pharmacology approaches, Trends in Pharmacological Sciences 43(4): 293-304.
- Fu Y., Taghvafard H., Said M.M., Rossman E.I., Collins T.A., Billiald-Desquand S., Leishman D., Graaf P.H. van der, Hasselt J.G.C. van & Snelder N. (2022), A novel cardiovascular systems model to quantify drugs effects on the inter‐relationship between contractility and other hemodynamic variables, CPT: Pharmacometrics and Systems Pharmacology 11(5): 640-652.
- Liu F., Aulin L.B.S., Guo T., Krekels E.H.J., Moerland M., Graaf P.H. van der & Hasselt J.G.C. van (2022), Modelling inflammatory biomarker dynamics in a human lipopolysaccharide (LPS) challenge study using delay differential equations, British Journal of Clinical Pharmacology 88(12): 5420-5427.
- Liu F., Aulin L.B.S., Kossen S.S.A., Cathalina J.E.J., Bremmer M., Foks A.C., Graaf P.H. van den Moerland M. & Hasselt J.G.C. van (2022), A system pharmacology Boolean network model for the TLR4-mediated inflammatory response in early sepsis, Journal of Pharmacokinetics and Pharmacodynamics 49(6): 645-655.
- Holstein S.A., Venkatakrishnan K. & Graaf P.H. van der (2022), Quantitative clinical pharmacology of CAR T‐cell therapy, Clinical Pharmacology & Therapeutics 112(1): 11-15.
- Graaf P.H. van der (2022), Diversity in clinical pharmacology coming of age, Clinical Pharmacology & Therapeutics 112(2): 191-193.
- Venkatakrishnan K. & Graaf P.H. van der (2022), Toward project optimus for oncology precision medicine: multi-dimensional dose optimization enabled by quantitative clinical pharmacology, Clinical Pharmacology & Therapeutics 112(5): 927-932.
- Aulin L.B.S., Tandar S.T., Zijp T. van, Ballegooie E. van, Graaf P.H. van der, Saleh M.A.A.E.W., Välitalo P. & Hasselt J.G.C. van (2022), Physiologically based modelling framework for prediction of pulmonary pharmacokinetics of antimicrobial target site concentrations, Clinical Pharmacokinetics 61: 1735-1748.
- Mehta K.M., Guo T., Wallis R.S., Graaf P.H. van der & Hasselt J.G.C. van (2022), Quantitative systems pharmacology modeling framework of autophagy in tuberculosis: application to adjunctive metformin host-directed therapy, Antimicrobial Agents and Chemotherapy 66(8): e0036622.
- Sher A., Niederer S.A., Mirams G.R., Kirpichnikova A., Allen R., Mathmanathan P., Gavaghan D.J., Graaf P.H. van der & Noble D. (2022), A Quantitative Systems Pharmacology perspective on the importance of parameter identifiability, Bulletin of Mathematical Biology 84(3): 39.
- Peck R.W., Holstein S.A. & Graaf P.H. van der (2022), BIA 10‐2474: some lessons are clear but important questions remain unanswered, Clinical Pharmacology & Therapeutics 111(2): 343-345.
- Seo S.K. & Graaf P.H. van der (2022), How a pandemic simultaneously strengthened existing fundamentals and drove new innovations in clinical pharmacology, Clinical Pharmacology & Therapeutics 112(6): 1141-1144.
- Desikan R., Padmanabhan P., Kierzek A.M. & Graag P.H. van der (2022), Mechanistic models of COVID-19: insights into disease progression, vaccines, and therapeutics, International Journal of Antimicrobial Agents 60(1): 106606.
- Chelliah V. & Graaf P.H. van der (2022), Model‐informed target identification and validation through combining quantitative systems pharmacology with network‐based analysis, CPT: Pharmacometrics and Systems Pharmacology 11(4): 399-402.
- Graaf P.H. van der (2022), Probability of success in drug development, Clinical Pharmacology & Therapeutics 111(5): 983-985.
- Giacomini K.M. & Graaf P.H. van der (2022), The pandemic as a catalyst for disruptive innovation in clinical pharmacology, Clinical Pharmacology & Therapeutics 111(3): 529-532.
- Minichmayr I.K., Ravenstein P., Graaf P.H. van der & Vamvakas S. (2022), Therapeutic innovations in neuroscience: what’s new on the horizon?, Clinical Pharmacology & Therapeutics 111(4): 715-717.
- Aulin L.B.S., Lange D.W. de, Saleh M.A.A., Graaf P.H. van der, Völler S. & Hasselt J.G.C. (2021), Biomarker-guided individualization of antibiotic therapy, Clinical Pharmacology & Therapeutics 110(2): 346-360.
- Aulin L.B.S., Liakopoulos A., Graaf P.H. van der, Rozen D.E. & Hasselt J.G.C. (2021), Design principles of collateral sensitivity-based dosing strategies, Nature Communications 12: 5691.
- Wijk R.C. van, Sar A.M. van der, Krekels E.H.J., Verboom T., Spaink H.P., Simonsson U.S.H. & Graaf P.H. van der (2020), Quantification of natural growth of two strains of Mycobacterium marinum for translational anti‐tuberculosis drug development, Clinical and Translational Science 13(6): 1060-1064.
- Wijk R.C. van, Hu W.B., Dijkema S.M., Berg D. van den, Liu J., Bahi R., Verbeek F.J., Simonsson U.S.H., Spaink H.P., Graaf P.H. van der & Krekels E.H.J. (2020), Anti-tuberculosis effect of isoniazid scales accurately from zebrafish to humans, British Journal of Pharmacology 177(24): 5518-5533.
- Fu Y., Snelder N., Graaf P.H. van der & Hasselt J.G.C. van (2020), Hemodynamic simulator: a shiny web application for predicting drug effect on hemodynamics, Journal of Pharmacological and Toxicological Methods 105: 23.
- Krekels E.H.J., Calvier E.A.M., Graaf P.H. van der & Knibbe C.A.J. (2019), Children Are Not Small Adults, but Can We Treat Them As Such?, CPT: Pharmacometrics and Systems Pharmacology 8(1): 34-38.
- Wijk R.C. van, Krekels E.H.J., Kantae V., Harms A.C., Hankemeier T., Graaf P.H. van der & Spaink H.P. (2019), Impact of post-hatching maturation on the pharmacokinetics of paracetamol in zebrafish larvae, Scientific Reports 9: 2149.
- Wijk R.C. van, Krekels E.H.J., Kantae V., Ordas A., Kreling T., Harms A.C., Hankemeier T., Spaink H.P. & Graaf P.H. van der (2019), Mechanistic and quantitative understanding of pharmacokinetics in zebrafish larvae through nanoscale blood sampling and metabolite modelling of paracetamol, Journal of Pharmacology and Experimental Therapeutics 371(1): 15-24.
- Schulthess P., Rottschäfer V., Yates J.W.T. & Graaf P.H. van der (2019), Optimization of cancer treatment in the frequency domain, AAPS Journal 21(6): 106.
- 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.
- Yin A., Yamada A., Stam W.B., Hasselt J.G.C. van & Graaf P.H. van der (2018), Quantitative systems pharmacology analysis of drug combination and scaling to humans: the interaction between noradrenaline and vasopressin in vasoconstriction, British Journal of Pharmacology 175(16): 3394-3406.
- Aulin L.B.S., Valitalo P.A., Rizk M.L., Visser S.A.G., Rao G., Graaf P.H. van der & Hasselt J.G.C. van (2018), Validation of a Model Predicting Anti-infective Lung Penetration in the Epithelial Lining Fluid of Humans, Pharmaceutical Research 35(2): 26.
- Schulthess P., Post T.M., Yates J.W.T. & Graaf P.H. van der (2018), Frequency-Domain Response Analysis for Quantitative Systems Pharmacology Models, CPT: Pharmacometrics and Systems Pharmacology 7(2): 111-123.
- Ramamoorthy A., Sadler B.M., Hasselt J.G.C. van, Elassaiss J., Kasichayanula S, Edwards A.Y., Graaf P.H. van der, Zhang L & Wagner J.A. (2018), Crowdsourced Asparagus Urinary Odor Population Kinetics, CPT: Pharmacometrics and Systems Pharmacology 7(1): 34-41.
- Calvier E.A.M., Krekels E.H.J., Yu H., Välitalo P.A.J., Johnson T.N., Rostami-Hodjegan A., Tibboel D., Graaf P.H. van der, Danhof M. & Knibbe C.A.J. (2018), Drugs Being Eliminated via the Same Pathway Will Not Always Require Similar Pediatric Dose Adjustments, CPT: Pharmacometrics and Systems Pharmacology 7(3): 175-185.
- Schulthess P., Wijk R.C. van, Krekels E.H.J., Yates J.W.T., Spaink H.P. & Graaf P.H. van der (2018), Outside-in systems pharmacology combines innovative computational methods with high-throughput whole vertebrate studies, CPT: Pharmacometrics and Systems Pharmacology 7(5): 285-287.
- 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.
- 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.
- Esdonk M.J. van, Zutphen E.J.M. van, Roelfsema F., Pereira A.M., Graaf P.H. van der, Biermasz N.R., Stevens J. & Burggraaf J. (2018), How are growth hormone and insulin-like growth factor-1 reported as markers for drug effectiveness in clinical acromegaly research? A comprehensive methodologic review, Pituitary 21(3): 310-322.
- 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.
- 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.
- Kantae V., Krekels E.H.J., Esdonk M.J. van, Lindenburg P.W., Harms A.C., Knibbe C.A.J., Graaf P.H. van der & Hankemeier T. (2017), Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy, Metabolomics 13(1): 9.
- 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.
- Wijk R.C. van, Krekels E.H.J., Hankemeier T., Spaink H.P. & Graaf P.H. van der (2017), Systems pharmacology of hepatic metabolism in zebrafish larvae, Drug Discovery Today: Disease Models 22: 27-34.
- 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.
- Esdonk M.J. van, Burggraaf J., Graaf P.H. van der & Stevens J. (2017), A two-step deconvolution-analysis-informed population pharmacodynamic modeling approach for drugs targeting pulsatile endogenous compounds, Journal of Pharmacokinetics and Pharmacodynamics 44(4): 389-400.
- Kantae V., Krekels E.H.J., Esdonk M.J. van, Lindenburg P.W., Harms A.C., Knibbe C.A.J., Graaf P.H. van der & Hankemeier T. (2017), Integration of pharmacometabolomics with pharmacokinetics and pharmacodynamics: towards personalized drug therapy: an addition to the topical collection "Recent Advances in Pharmacometabolomics: Enabling Tools for Precision Medicine", Metabolomics 13(5): 58.
- 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.
- 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.
- 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.
- Kohler I., Hankemeier T., Graaf P.H. van der, Knibbe C.A.J. & Hasselt J.G.C. van (2017), Integrating clinical metabolomics-based biomarker discovery and clinical pharmacology to enable precision medicine, European Journal of Pharmaceutical Sciences 109: S15-S21.
- Goulooze S.C., Krekels E.H.J., Dijk M. van, Tibboel D., Graaf P.H. van der, Hankemeier T., Knibbe C.A.J. & Hasselt J.G.C. van (2017), Towards personalized treatment of pain using a quantitative systems pharmacology approach, European Journal of Pharmaceutical Sciences 109: S32-S38.
- Guo Y., Wijk R.C. van, Krekels E.H.J., Spaink H.P., Graaf P.H. van der & Verbeek F.J. (2017), Multi-modal 3D reconstruction and measurements of zebrafish larvae and its organs using axial-view microscopy, 2017 IEEE International conference on image processing (ICIP). IEEE International Conference on Image Processing 2017 17 September 2017 - 20 September 2017: IEEE Xplore. 2194-2198.
- Graaf P.H. van der, Benson N. & Peletier L.A. (2016), Topics in Mathematical Pharmacology, Journal of Dynamics and Differential Equations 28(3-4): 1337-1356.
- Hasselt J.G. van, Rizk M.L., Lala M., Chavez-Eng C., Visser S.A., Kerbusch T., Danhof M., Rao G. & Graaf P.H. van der (2016), Pooled population pharmacokinetic model of imipenem in plasma and the lung epithelial lining fluid, British Journal of Clinical Pharmacology 81: 1113–1123.
- Kantae V., Krekels E.H.J., Ordas A.K., Gonzalez O., Wijk R.C. van, Harms A.C., Racz P.I., Graaf P.H. van der, Spaink H.P. & Hankemeier T. (2016), Pharmacokinetic modeling of paracetamol uptake and clearance in zebrafish larvae: expanding the allometric scale in vertebrates with five orders of magnitude, Zebrafish 13(6): 504-510.
- 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.
- Valitalo P.A.J., Griffioen K., Rizk M., Visser S., Danhof M., Rao M., Graaf P. & Hasselt J.G.C. van (2016), Structure-based prediction of anti-infective drug concentrations in the human lung epithelial lining fluid, Pharmaceutical Research 33(4): 856-867.
- 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.
- Spaink H., Racz P., Ordas A., Veneman W., Vijver M., Wildwater M., Pieters R., Zope H.R., Kros A., Kantae V., Krekels E., Graaf P.H. van der & Hankemeier T. (2015), Automated zebrafish toxicology screening: effect assessment and uptake studies, Toxicology Letters 238(2): S54-S54.
- Vicini P. & Graaf P.H. van der (2013), Systems Pharmacology for Drug Discovery and Development: Paradigm Shift or Flash in the Pan?, Clinical Pharmacology & Therapeutics 93(5): 379-381.
- Milligan P.A., Brown M.J., Marchant B., Martin S.W., Graaf P.H. van der, Benson N., Nucci G., Nichols D.J., Boyd R.A., Mandema J.W., Krishnaswami S., Zwillich S., Gruben D., Anziano R.J., Stock T.C. & Lalonde R.L. (2013), Model-Based Drug Development: A Rational Approach to Efficiently Accelerate Drug Development, Clinical Pharmacology & Therapeutics 93(6): 502-514.
- Roeblitz S., Stoetzel C., Deuflhard P., Jones H.M., Azulay D.-O., Graaf P.H. van der & Martin S.W. (2013), A mathematical model of the human menstrual cycle for the administration of GnRH analogues, Journal of Theoretical Biology 321: 8-27.
- Germani M., Del Bene F., Rocchetti M. & Graaf P.H. van der (2013), A4S: A user-friendly graphical tool for pharmacokinetic and pharmacodynamic (PK/PD) simulation, Computer Methods and Programs in Biomedicine 110(2): 203-214.
- 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.
- Peletier L.A., Benson N. & Graaf P.H. van der (2010), Impact of protein binding on receptor occupancy: A two-compartment model, 265: 657-671.
- Peletier L.A., Benson N. & Graaf P.H. van der (2009), Impact of plasma-protein binding on receptor occupancy: An analytical description, 256: 253-262.
- Zuideveld K.P., Graaf P.H. van der, Peletier L.A. & Danhof M. (2007), Allometric scaling of pharmacodynamic responses: application to 5-Ht1A receptor mediated responses from rat to man, PHARMACEUTICAL RESEARCH 24(11): 2031-2039.
- Jonker D.M., Visser S.A.G., Graaf P.H. van der, Voskuyl R.A. & Danhof M. (2005), Towards a mechanism-based analysis of pharmacodynamic drug-drug interactions in vivo, Pharmacology and Therapeutics 106(1): 1-18.
- Jonker D.M., Visser S.A.G., Graaf P.H. van der, Voskuyl R.A. & Danhof M. (2005), Towards a mechanism-based analysis of pharmacodynamic drug-drug interactions in vivo, Pharmacology and Therapeutics 106(1): 1-18.
- Zuideveld K.P., Graaf P.H. van der, Newgreen D., Thurlow R., Petty N., Jordan P., Peletier L.A. & Danhof M. (2004), Mechanism-based pharmacokinetic/pharmacodynamic modeling of 5-HT1A receptor agonists: estimation of in vivo affinity and intrinsic efficacy on body termperature in rats, Journal of Pharmacology and Experimental Therapeutics 308: 1012-1020.
- Danhof M., Graaf P.H. van der, Visser S.A.G. & Zuideveld K.P. (2004), Mechanism-based pharmacodynamic modelling for prediction of exposure response. In: D'Argenio D.Z. (Ed.), Advanced Methods of Pharmacokinetic & Pharmacodynamic Systems Analysis. Boston: Kluwer Academic Publishers. 49-65.
- Visser S.A.G., Wolters F.L.C., Gubbens-Stibbe J.M., Tukker E., Graaf P.H. van der, Peletier L.A. & Danhof M. (2003), Mechanism-based pharmacokinetic/pharmacodynamic modeling of the electroencephalogram effects of GABAA receptor modulators: in vitro-in vivo correlations, Journal of Pharmacology and Experimental Therapeutics 304(1): 88-101.
- Visser S.A.G., Gubbens-Stibbe J.M., Graaf P.H. van der, Danhof M. & Peletier L.A. (2003), Mechanism-based Pharmacokinetic/Pharmacodynamic modeling of the electroencephalogram effects of GABAA receptor modulators: in viro-in vivi modulators, Journal of Pharmacology and Experimental Therapeutics 304: 88-101.
- Visser S.A.G., Wolters F.L.C., Graaf P.H. van der, Peletier L.A. & Danhof M. (2003), Dose-Dependent EEG Effects of Zolpidem Provide Evidence for GABAA Receptor Subtype Selectivity in Vivo, Journal of Pharmacology and Experimental Therapeutics 304: 1251-1257.
- Visser S.A.G., Graaf P.H. van der, Danhof M. & Peletier L.A. (2003), Mechanism-Based Modeling of the Pharmacodynamic Interaction of Alphaxalone and Midazolam in Rats, Journal of Pharmacology and Experimental Therapeutics 307: 765-775.
- Zuideveld K.P., Rusic-Pavletic J., Maas J., Peletier L.A., Graaf P.H. van der & Danhof M. (2002), Pharmacokinetic-Pharmacodynamic modeling of buspirone and its metabolite 1-(2-Pyrimidinyl)-Piperazine in rats, Journal of Pharmacology and Experimental Therapeutics 303: 1130-1137.
- Zuideveld K.P., Gestel A. van, Peletier L.A., Graaf P.H. van der & Danhof M. (2002), Pharmacokinetic-pharmacodynamic modelling of the hypothermic and corticosterone effects of the 5-HT1A-receptor agonist flesinoxan, European Journal of Pharmacology 445: 43-54.
- Lorenzen A., Beukers M.W., Graaf P.H. van der, Lang H., Muijlwijk-Koezen J.E. van, Groote M. de, Menge W., Schwabe U. & IJzerman A.P. (2002), Modulation of agonist responses at the A1 adenosine receptor by an irreversible antagonist, receptor-G protein uncoupling and by the G protein activation state, Biochemical Pharmacology 64: 1251-1265.
- Visser S.A.G., Gladdines W.W.F.T., Graaf P.H. van der, Peletier L.A. & Danhof M. (2002), Neuroactive steroids differ in potency but not in intrinsic efficacy at the GABAA receptor in vivo, Journal of Pharmacology and Experimental Therapeutics 303: 616-626.
- Visser S.A.G., Wolters F.L.C., Gubbens-Stibbe J.M., Tukker H.E., Graaf P.H. van der & Peletier L.A. (2002), Mechanism-based Pharmacokinetic-Pharmacodynamic Modelling the electroencephalogram effects of GABAA receptor modulators: in vitro – in vivo correlations, Journal of Pharmacology and Experimental Therapeutics 304: 88-101.
- Zuideveld K.P., Treijtel N., Maas H.J., Gubbens-Stibbe J.M., Peletier L.A., Graaf P.H. van der & Danhof M. (2002), A competitive interaction model predicts the effect of WAY-100,635 on the Time Course of R-(+)-8-Hydroxy-2-(di-n-propylamino)tetralin-Induced Hypothermia, Journal of Pharmacology and Experimental Therapeutics 300: 330-338.
- Visser S.A.G., Smulders J.G.M., Reijers B.P.R., Graaf P.H. van der, Peletier L.A. & Danhof M. (2002), Mechanism-based pharmacokinetic-pharmacodynamic modelling of concentration-dependent hysteresis and biphasic electroencephalogram effects of alphaxalone in rats, Journal of Pharmacology and Experimental Therapeutics 302: 1158-1167.
- Cleton A., Graaf P.H. van der, Ghijsen W., Voskuyl R.A. & Danhof M. (1999), Mechanism-based modeling of adaptive changes in the pharmacodynamics of midazolam in the kindling model of epilepsy, PHARMACEUTICAL RESEARCH 16: 1702-1709.
- Graaf P.H. van der, Nilsson J., Schaick E.A. van & Danhof M. (1999), Multivariate quantitative structure-pharmacokinetic relationships (QSPKR) analysis of adenosine A1 receptor agonists in rat, JOURNAL OF PHARMACEUTICAL SCIENCES 88: 306-312.
- Graaf P.H. van der, Schaick E.A. van, Visser S.A.G., Greef H.J.M.M. de, IJzerman A.P. & Danhof M. (1998), Mechanism-based pharmacokinetic-pharmacodynamic modeling of anti-lipolytic effects of adenosine A1 receptor agonists in rats: prediction of tissue-dependent efficay in vivo, Journal of Pharmacology and Experimental Therapeutics : .
- Cleton A., Graaf P.H. van der, Voskuyl R.A. & Danhof M. (1998), Mechanism-based modelling of the adaptive changes in the pharmacodynamics of midazolan in rats with experimentally induced epilepsy. In: Danhof M. & Steimer J.L. (Eds.), Measurements and kinetics of in vivo drug effects. Advances in simultaneous pharmacokinetic pharmacodynamic modelling. Leiden: LACDR.
- Stam W.B., Graaf P.H. van der & Saxena P.R. (1998), Functional characterization of the pharmacological profile of the putative a1B-adrenoceptor antagonist, (+)-cyclazosin, European Journal of Pharmacology 361: 79-83.
- Cox E.H., Kerbusch T., Graaf P.H. van der & Danhof M. (1998), Pharmacokinetic-pharmacodynamic modeling of the electroencephalogram effect of synthetic opioids in the rat: correlation with the interaction at the m-opioid receptor, Journal of Pharmacology and Experimental Therapeutics 284(3): 1095-1103.
- Stam W.B., Graaf P.H. van der & Saxena P.R. (1998), Characterization of receptors mediating contraction of the rat isolated small mesenteric artery and aorta to arginine vasopressin and oxytocin, British Journal of Pharmacology 125: 865-873.
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