Meindert Danhof

Summary

Affiliation: Leiden University
Country: The Netherlands

Publications

  1. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling-a new classification of biomarkers
    Meindert Danhof
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Pharm Res 22:1432-7. 2005
  2. ncbi request reprint 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
    Elizabeth C M de Lange
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden, The Netherlands
    Clin Pharmacokinet 41:691-703. 2002
  3. ncbi request reprint Markers of disease severity in chronic obstructive pulmonary disease
    Luigi G Franciosi
    Gorlaeus Laboratories, Leiden Amsterdam Center for Drug Research, Leiden University, The Netherlands
    Pulm Pharmacol Ther 19:189-99. 2006
  4. ncbi request reprint Disease system analysis: basic disease progression models in degenerative disease
    Teun M Post
    Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands
    Pharm Res 22:1038-49. 2005
  5. pmc Pharmacokinetic-pharmacodynamic modeling of the effectiveness and safety of buprenorphine and fentanyl in rats
    Ashraf Yassen
    Division of Pharmacology, Gorlaeus Laboratories, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Pharm Res 25:183-93. 2008
  6. doi request reprint Systems pharmacology - Towards the modeling of network interactions
    Meindert Danhof
    Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, P O Box 9502, 2300 RA Leiden, The Netherlands Electronic address
    Eur J Pharm Sci 94:4-14. 2016
  7. pmc Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models
    Meindert Danhof
    Leiden Academic Centre for Drug Research, Leiden University, P O Box 9502, 2300 RA, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 42:447-62. 2015
  8. pmc Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease
    Paulien Gm Ravenstijn
    Division of Pharmacology, LACDR Leiden University, Leiden, The Netherlands
    Fluids Barriers CNS 9:4. 2012
  9. pmc Extensions to the visual predictive check to facilitate model performance evaluation
    Teun M Post
    NV Organon, Oss, The Netherlands
    J Pharmacokinet Pharmacodyn 35:185-202. 2008
  10. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis
    Meindert Danhof
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands
    Annu Rev Pharmacol Toxicol 47:357-400. 2007

Detail Information

Publications107 found, 100 shown here

  1. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling-a new classification of biomarkers
    Meindert Danhof
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Pharm Res 22:1432-7. 2005
    ..In this paper, the use of the new biomarker classification is discussed in the context of the application of mechanism-based PK/PD analysis in drug discovery and development...
  2. ncbi request reprint 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
    Elizabeth C M de Lange
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Sylvius Laboratories, Leiden, The Netherlands
    Clin Pharmacokinet 41:691-703. 2002
    ..As non-invasive alternative techniques, positron emission tomography or magnetic resonance spectroscopy may be of added value...
  3. ncbi request reprint Markers of disease severity in chronic obstructive pulmonary disease
    Luigi G Franciosi
    Gorlaeus Laboratories, Leiden Amsterdam Center for Drug Research, Leiden University, The Netherlands
    Pulm Pharmacol Ther 19:189-99. 2006
    ....
  4. ncbi request reprint Disease system analysis: basic disease progression models in degenerative disease
    Teun M Post
    Leiden Experts on Advanced Pharmacokinetics and Pharmacodynamics, Leiden, The Netherlands
    Pharm Res 22:1038-49. 2005
    ..To describe the disease status of degenerative diseases (i.e., type 2 diabetes mellitus, Parkinson's disease) as function of disease process and treatment effects, a family of disease progression models is introduced...
  5. pmc Pharmacokinetic-pharmacodynamic modeling of the effectiveness and safety of buprenorphine and fentanyl in rats
    Ashraf Yassen
    Division of Pharmacology, Gorlaeus Laboratories, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Pharm Res 25:183-93. 2008
    ..The objective of this investigation was to characterize the relationship between buprenorphine or fentanyl exposure and the effectiveness and safety outcome in rats...
  6. doi request reprint Systems pharmacology - Towards the modeling of network interactions
    Meindert Danhof
    Systems Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Einsteinweg 55, P O Box 9502, 2300 RA Leiden, The Netherlands Electronic address
    Eur J Pharm Sci 94:4-14. 2016
    ....
  7. pmc Kinetics of drug action in disease states: towards physiology-based pharmacodynamic (PBPD) models
    Meindert Danhof
    Leiden Academic Centre for Drug Research, Leiden University, P O Box 9502, 2300 RA, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 42:447-62. 2015
    ..Pertinent processes on the causal path are: (1) target site distribution, (2) target binding and activation and (3) transduction and homeostatic feedback. ..
  8. pmc Evaluation of blood-brain barrier transport and CNS drug metabolism in diseased and control brain after intravenous L-DOPA in a unilateral rat model of Parkinson's disease
    Paulien Gm Ravenstijn
    Division of Pharmacology, LACDR Leiden University, Leiden, The Netherlands
    Fluids Barriers CNS 9:4. 2012
    ..This study aimed to investigate BBB transport of L-DOPA transport in conjunction with its intra-brain conversion, in both control and diseased cerebral hemispheres in the unilateral rat rotenone model of Parkinson's disease...
  9. pmc Extensions to the visual predictive check to facilitate model performance evaluation
    Teun M Post
    NV Organon, Oss, The Netherlands
    J Pharmacokinet Pharmacodyn 35:185-202. 2008
    ..The proposed extensions to the VPC are illustrated by a pharmacokinetic simulation example and applied to a pharmacodynamic disease progression example...
  10. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling: biophase distribution, receptor theory, and dynamical systems analysis
    Meindert Danhof
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA Leiden, The Netherlands
    Annu Rev Pharmacol Toxicol 47:357-400. 2007
    ..This has yielded models with much-improved properties for extrapolation and prediction. These models constitute a theoretical basis for rational drug discovery and development...
  11. doi request reprint Mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling in translational drug research
    Meindert Danhof
    Leiden University, Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Einsteinweg 55, PO Box 9503, 2300 RA Leiden, The Netherlands
    Trends Pharmacol Sci 29:186-91. 2008
    ..In this review, the principles of mechanism-based PK-PD modeling are described and illustrated by recent applications...
  12. pmc Explaining variability in ciclosporin exposure in adult kidney transplant recipients
    Rogier R Press
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands
    Eur J Clin Pharmacol 66:579-90. 2010
    ..Therefore, this study is aimed at identifying a relationship between genetic polymorphisms and the variability in CsA exposure, while accounting for non-genetic sources of variability...
  13. ncbi request reprint Compartmental modeling of transdermal iontophoretic transport: I. In vitro model derivation and application
    Akhmad Kharis Nugroho
    Leiden Amsterdam Center for Drug Research, 2300 RA Leiden, The Netherlands
    Pharm Res 21:1974-84. 2004
    ..The objective of this study was to develop a family of compartmental models to describe in a strictly quantitative manner the transdermal iontophoretic transport of drugs in vitro...
  14. ncbi request reprint Targeting liposomes with protein drugs to the blood-brain barrier in vitro
    Corine C Visser
    Leiden Amsterdam Centre for Drug Research LACDR, Leiden University, Division of Pharmacology, PO Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharm Sci 25:299-305. 2005
    ..Our experiments suggest that liposomes release some of their content within the BBB, making targeting of liposomes to the TfR on BCEC an attractive approach for brain drug delivery...
  15. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modelling of the reversal of buprenorphine-induced respiratory depression by naloxone : a study in healthy volunteers
    Ashraf Yassen
    Division of Pharmacology, Leiden Amsterdam Centre for Drug Research, Leiden, The Netherlands
    Clin Pharmacokinet 46:965-80. 2007
    ..The aim of this study was to characterise the pharmacodynamic interaction between buprenorphine and naloxone in healthy volunteers...
  16. doi request reprint Changes in GABAA receptor properties in amygdala kindled animals: in vivo studies using [11C]flumazenil and positron emission tomography
    Lia C Liefaard
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Epilepsia 50:88-98. 2009
    ..The purpose of the present investigation was to quantify alterations in GABA(A) receptor density in vivo in rats subjected to amygdala kindling...
  17. doi request reprint Differences in the sensitivity of behavioural measures of pain to the selectivity of cyclo-oxygenase inhibitors
    Dymphy R H Huntjens
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, P O Box 9503, 2300 RA, Leiden, The Netherlands
    Eur J Pain 13:448-57. 2009
    ..We also assess prostaglandin (PGE(2)) and thromboxane (TXB(2)) inhibition to establish the correlation between behavioural measures and the degree of selectivity for COX-1 and COX-2...
  18. doi request reprint Pharmacokinetic-pharmacodynamic analysis of the static allodynia response to pregabalin and sildenafil in a rat model of neuropathic pain
    Gregor Bender
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    J Pharmacol Exp Ther 334:599-608. 2010
    ..4% (42.3-66.9%) decrease in EC(50), whereas the percentage-transformed PD model demonstrated a 53.5% (42.7-64.3%) shift. It is concluded from these studies that there is a synergistic PD interaction between pregabalin and sildenafil...
  19. doi request reprint Pharmacokinetic/pharmacodynamic modelling of the EEG effects of opioids: the role of complex biophase distribution kinetics
    Dorien Groenendaal
    Leiden Amsterdam Center for Drug Research, Leiden University, Division of Pharmacology, PO Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharm Sci 34:149-63. 2008
    ....
  20. ncbi request reprint Pharmacokinetic/pharmacodynamic modelling of the anti-hyperalgesic and anti-nociceptive effect of adenosine A1 receptor partial agonists in neuropathic pain
    Marloes P Schaddelee
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, P O Box 9502, 2300 RA, Leiden, The Netherlands
    Eur J Pharmacol 514:131-40. 2005
    ..microl/ng, respectively, versus 55+/-8 g microl/ng for 5'dCPA. Adenosine A1 receptor partial agonists behave as full agonists with regard to the anti-hyperalgesic effect in neuropathic pain, but the anti-nociceptive effect is diminished...
  21. pmc Markers of exacerbation severity in chronic obstructive pulmonary disease
    Luigi G Franciosi
    Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
    Respir Res 7:74. 2006
    ..In an attempt to find the best surrogates for exacerbations, we have reviewed the literature to identify which of these markers change in a consistent manner with the severity of the exacerbation event...
  22. doi request reprint Mechanistic studies of the transdermal iontophoretic delivery of 5-OH-DPAT in vitro
    Oliver W Ackaert
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, Einsteinweg 55, 2333 CC Leiden, The Netherlands
    J Pharm Sci 99:275-85. 2010
    ..0 micromol x cm(-2) h(-1) demonstrating the potential of the iontophoretic delivery of this dopamine agonist for the symptomatic treatment of Parkinson's disease...
  23. doi request reprint Transdermal iontophoretic delivery of a novel series of dopamine agonists in vitro: physicochemical considerations
    Oliver W Ackaert
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    J Pharm Pharmacol 62:709-20. 2010
    ..The transdermal iontophoretic delivery of a novel series of 2- aminotetralins and chromanamine-based dopamine agonists was investigated in vitro...
  24. doi request reprint The pharmacokinetics and pharmacological effect of (S)-5-OH-DPAT following controlled delivery with transdermal iontophoresis
    Oliver W Ackaert
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    J Pharm Sci 100:2996-3009. 2011
    ..Finally, PK-PD analysis revealed that steady delivery rates are translated into continuous dopaminergic stimulation. This can be of benefit for reducing side effects in the symptomatic treatment of Parkinson's disease with 5-OH-DPAT...
  25. ncbi request reprint Blood-brain barrier transport of synthetic adenosine A1 receptor agonists in vitro: structure transport relationships
    Marloes P Schaddelee
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, P O Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharm Sci 20:347-56. 2003
    ..In addition, transport by the es nucleoside transporter may contribute to the transport of certain structurally distinct analogues...
  26. pmc Pharmacokinetic modeling of non-linear brain distribution of fluvoxamine in the rat
    Marian Geldof
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, PO Box 9502, 2300 RA, Leiden, The Netherlands
    Pharm Res 25:792-804. 2008
    ..A pharmacokinetic (PK) model is proposed for estimation of total and free brain concentrations of fluvoxamine...
  27. ncbi request reprint Predictive Performance of a Recently Developed Population Pharmacokinetic Model for Morphine and its Metabolites in New Datasets of (Preterm) Neonates, Infants and Children
    Elke H J Krekels
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Clin Pharmacokinet 50:51-63. 2011
    ....
  28. ncbi request reprint Pharmacodynamic analysis of the anticonvulsant effects of tiagabine and lamotrigine in combination in the rat
    Daniël M Jonker
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, Leiden, The Netherlands
    Epilepsia 45:424-35. 2004
    ..The pharmacodynamic interaction between the antiepileptic drugs (AEDs) tiagabine (TGB) and lamotrigine (LTG) was characterized on basis of the anticonvulsant effect in the cortical stimulation model in the rat...
  29. ncbi request reprint Transdermal iontophoresis of rotigotine across human stratum corneum in vitro: influence of pH and NaCl concentration
    Akhmad Kharis Nugroho
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, 2300 RA Leiden, The Netherlands
    Pharm Res 21:844-50. 2004
    ..The aim of this study was to characterize the influence of pH and NaCl concentration on the transdermal iontophoretic transport of the dopamine receptor agonist rotigotine across human stratum corneum (HSC)...
  30. ncbi request reprint Synergistic combinations of anticonvulsant agents: what is the evidence from animal experiments?
    Daniël M Jonker
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, Leiden, The Netherlands
    Epilepsia 48:412-34. 2007
    ....
  31. ncbi request reprint Population pharmacokinetic model of fluvoxamine in rats: utility for application in animal behavioral studies
    Marian Geldof
    Division of Pharmacology, LACDR, Leiden University, P O Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharm Sci 30:45-55. 2007
    ..By using the pertinent information from the population PK model, individual PK profiles and the PK/PD correlation could be adequately described...
  32. pmc Adaptive trials in paediatric development: dealing with heterogeneity and uncertainty in pharmacokinetic differences in children
    Massimo Cella
    LACDR, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Br J Clin Pharmacol 74:346-53. 2012
    ..To assess whether an adaptive design in early clinical trials based on the paradigm of variable dosing and controlled exposure can provide better dosing recommendations compared with the standard fixed dose approach...
  33. pmc A bodyweight-dependent allometric exponent for scaling clearance across the human life-span
    Chenguang Wang
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Pharm Res 29:1570-81. 2012
    ..To explore different allometric equations for scaling clearance across the human life-span using propofol as a model drug...
  34. doi request reprint Maturation of the glomerular filtration rate in neonates, as reflected by amikacin clearance
    Roosmarijn F W De Cock
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Clin Pharmacokinet 51:105-17. 2012
    ..The model was used to derive a rational dosing regimen in comparison with currently used dosing regimens for amikacin...
  35. ncbi request reprint Pharmacokinetic-pharmacodynamic modelling of the hypothermic and corticosterone effects of the 5-HT1A receptor agonist flesinoxan
    Klaas P Zuideveld
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Gorlaeus Laboratory, P O Box 9502, 2300 RA, Leiden, The Netherlands
    Eur J Pharmacol 445:43-54. 2002
    ..Furthermore, the similarity in potency between the hypothermic and corticosterone effects suggests that both are mediated via tissues with a similar receptor-effector coupling efficiency...
  36. ncbi request reprint Pharmacokinetic-pharmacodynamic modeling of the respiratory depressant effect of norbuprenorphine in rats
    Ashraf Yassen
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, P O Box 9502, 2300 RA Leiden, The Netherlands
    J Pharmacol Exp Ther 321:598-607. 2007
    ..By simulation it is shown that following i.v. administration of buprenorphine, the concentrations of norbuprenorphine reach values that are well below the values causing an effect on respiration...
  37. doi request reprint Evaluation of treatment response in depression studies using a Bayesian parametric cure rate model
    Gijs Santen
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, The Netherlands
    J Psychiatr Res 42:1189-97. 2008
    ..The method contrasts with the long-established snapshot on changes from baseline, as it incorporates the time course of response throughout treatment...
  38. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling of the respiratory-depressant effect of buprenorphine and fentanyl in rats
    Ashraf Yassen
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, P O Box 9502, 2300 RA Leiden, The Netherlands
    J Pharmacol Exp Ther 319:682-92. 2006
    ..As a result, the mechanism-based PK/PD model of fentanyl could be reduced to a biophase distribution model with fractional sigmoid E(max) pharmacodynamic model...
  39. ncbi request reprint Towards a mechanism-based analysis of pharmacodynamic drug-drug interactions in vivo
    Daniël M Jonker
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, P O Box 9502, 2300 RA, Leiden, The Netherlands
    Pharmacol Ther 106:1-18. 2005
    ..The in vivo application of operational models with advanced response surface modelling techniques will facilitate the rational development of synergistic drug combinations...
  40. doi request reprint Developmental changes in morphine clearance across the entire paediatric age range are best described by a bodyweight-dependent exponent model
    Chenguang Wang
    LACDR, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Clin Drug Investig 33:523-34. 2013
    ..The aim of the current study was to characterize the developmental changes in morphine clearance across the entire paediatric age range...
  41. doi request reprint Mechanism-based PK-PD model for the prolactin biological system response following an acute dopamine inhibition challenge: quantitative extrapolation to humans
    Jasper Stevens
    Division of Pharmacology, Gorlaeus Laboratories, Leiden Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, 2333 CC, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 39:463-77. 2012
    ..The PK-PD model successfully predicted the system prolactin response in humans, indicating that positive feedback on prolactin synthesis and allometric scaling thereof could be a new feature in describing complex homeostatic mechanisms...
  42. pmc First dose in children: physiological insights into pharmacokinetic scaling approaches and their implications in paediatric drug development
    Ashley Strougo
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, Einsteinweg, 55, P O Box 9502, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 39:195-203. 2012
    ..This highlights the necessity of investigating methodological uncertainty to allow a proper estimation of the "first dose in children" and assessment of its risk and benefits...
  43. doi request reprint Systemic and direct nose-to-brain transport pharmacokinetic model for remoxipride after intravenous and intranasal administration
    Jasper Stevens
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
    Drug Metab Dispos 39:2275-82. 2011
    ..Describing remoxipride pharmacokinetics at the target site (brain ECF) in a semiphysiology-based manner would allow for better prediction of pharmacodynamic effects...
  44. ncbi request reprint Pharmacokinetic-pharmacodynamic modeling of buspirone and its metabolite 1-(2-pyrimidinyl)-piperazine in rats
    Klaas P Zuideveld
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, Leiden, The Netherlands
    J Pharmacol Exp Ther 303:1130-7. 2002
    ....
  45. ncbi request reprint Transdermal iontophoresis of the dopamine agonist 5-OH-DPAT in human skin in vitro
    Akhmad Kharis Nugroho
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, University of Leiden, PO Box 9502, 2300 RA Leiden, The Netherlands
    J Control Release 103:393-403. 2005
    ..Thus, based on this in vitro study, transdermal iontophoretic delivery of 5-OH-DPAT is very promising...
  46. ncbi request reprint Decreased Efficacy of GABAA-receptor modulation by midazolam in the kainate model of temporal lobe epilepsy
    Lia C Liefaard
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Epilepsia 48:1378-87. 2007
    ..The changes in MDL efficacy were correlated to changes in ex vivo GABA(A)-receptor expression...
  47. ncbi request reprint Animal-to-human extrapolation of the pharmacokinetic and pharmacodynamic properties of buprenorphine
    Ashraf Yassen
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorleaus Laboratories, Leiden, The Netherlands
    Clin Pharmacokinet 46:433-47. 2007
    ..This investigation describes the interspecies scaling of the pharmacokinetics and pharmacodynamics of buprenorphine...
  48. ncbi request reprint Mechanism-based pharmacodynamic modeling of S(-)-atenolol: estimation of in vivo affinity for the beta1-adrenoceptor with an agonist-antagonist interaction model
    Tamara J van Steeg
    Leiden Amsterdam Center for Drug Research, Leiden University, Division of Pharmacology, PO Box 9502, 2300 RA Leiden, The Netherlands
    J Pharmacol Exp Ther 324:1234-42. 2008
    ..In conclusion, a meaningful estimate of in vivo affinity for S(-)-atenolol could be obtained using a mechanism-based pharmacodynamic modeling approach...
  49. doi request reprint Mechanistic model for the acute effect of fluvoxamine on 5-HT and 5-HIAA concentrations in rat frontal cortex
    Marian Geldof
    Division of Pharmacology, LACDR, Leiden University, P O Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharm Sci 33:217-29. 2008
    ..The model constitutes a useful basis for prediction of the time course of median 5-HT and 5-HIAA concentrations in the frontal cortex in behavioral pharmacology studies in vivo...
  50. ncbi request reprint Incorporating receptor theory in mechanism-based pharmacokinetic-pharmacodynamic (PK-PD) modeling
    Bart A Ploeger
    LAP and P Consultants BV, Leiden, The Netherlands
    Drug Metab Pharmacokinet 24:3-15. 2009
    ..This review provides an overview of recent developments in incorporating receptor theory in PK-PD modeling with a specific focus on the identifiability of these models...
  51. doi request reprint Sensitivity of the Montgomery Asberg Depression Rating Scale to response and its consequences for the assessment of efficacy
    Gijs Santen
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, P O Box 9502, 2300 Leiden, The Netherlands
    J Psychiatr Res 43:1049-56. 2009
    ..The selection of these subscales as primary endpoints in clinical trials could save over 1/3 in patients compared to the full HAMD whilst keeping the same statistical power...
  52. doi request reprint Impact of chronic inflammation on the pharmacokinetic-pharmacodynamic relationship of naproxen
    Dymphy R H Huntjens
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden University, Einsteinweg 55, PO Box 9503, 2300 RA, Leiden, The Netherlands
    Eur J Pain 14:227.e1-10. 2010
    ..In this study, we demonstrate the relevance of such a relationship for COX-inhibitors by modelling the effect of naproxen on prostaglandin E2 (PGE(2)) and thromboxane B2 (TXB(2)) in a chronic inflammation model in rats...
  53. doi request reprint Biomarker exposure-response relationships as the basis for rational dose selection: Lessons from a simulation exercise using a selective COX-2 inhibitor
    Amit Taneja
    Division of Pharmacology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands
    J Clin Pharmacol 56:609-21. 2016
    ..Simulations showed that dose-response discrimination occurred at doses higher than 150 mg, with predicted 60%-80% target engagement in the dose range of 150-400 mg. ..
  54. ncbi request reprint Iontophoretic R-apomorphine delivery in combination with surfactant pretreatment: in vitro validation studies
    Gai Ling Li
    Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, P O Box 9502, 2300 RA, Leiden, The Netherlands
    Int J Pharm 266:61-8. 2003
    ..A linear relationship between current density and R-apomorphine flux indicates that the iontophoretic delivery combined with surfactant pretreatment allows a controlled and individualised administration of R-apomorphine...
  55. ncbi request reprint Brain penetration of synthetic adenosine A1 receptor agonists in situ: role of the rENT1 nucleoside transporter and binding to blood constituents
    Marloes P Schaddelee
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, P O Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharm Sci 24:59-66. 2005
    ....
  56. ncbi request reprint The exploration of rotenone as a toxin for inducing Parkinson's disease in rats, for application in BBB transport and PK-PD experiments
    Paulien G M Ravenstijn
    Leiden Amsterdam Center for Drug Research, Leiden University, Division of Pharmacology, Leiden, The Netherlands
    J Pharmacol Toxicol Methods 57:114-30. 2008
    ....
  57. ncbi request reprint Relevance of absorption rate and lag time to the onset of action in migraine
    Hugo J Maas
    Leiden Amsterdam Center for Drug Research, Leiden University, Leiden, The Netherlands
    Clin Pharmacokinet 47:139-46. 2008
    ....
  58. doi request reprint Influence of feeding schedules on the chronobiology of renin activity, urinary electrolytes and blood pressure in dogs
    Jonathan P Mochel
    Department of Pharmacology, Leiden Academic Centre for Drug Research, Leiden, The Netherlands
    Chronobiol Int 31:715-30. 2014
    ..This synchronizing effect could be mediated by feeding-related signals, such as dietary sodium, capable of entraining circadian oscillators downstream of the master, light-dark-adjusted pacemaker in the suprachiasmatic nucleus. ..
  59. pmc Simultaneous pharmacokinetic modeling of gentamicin, tobramycin and vancomycin clearance from neonates to adults: towards a semi-physiological function for maturation in glomerular filtration
    Roosmarijn F W De Cock
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Pharm Res 31:2643-54. 2014
    ..Since glomerular filtration rate (GFR) is responsible for the elimination of a large number of water-soluble drugs, the aim of this study was to develop a semi-physiological function for GFR maturation from neonates to adults...
  60. pmc Not-in-trial simulation I: Bridging cardiovascular risk from clinical trials to real-life conditions
    Anne S Y Chain
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, 2300 RA, Leiden, The Netherlands Department of Medical Informatics, Erasmus Medical Centre, 3015 GE, Rotterdam, The Netherlands
    Br J Clin Pharmacol 76:964-72. 2013
    ..This study demonstrates the relevance of pharmacokinetic-pharmacodynamic (PKPD) relationships to characterize drug-induced QTc interval prolongation and explore the discrepancies between clinical trials and real-life conditions...
  61. pmc Covariate effects and population pharmacokinetics of lamivudine in HIV-infected children
    Chiara Piana
    LACDR, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Br J Clin Pharmacol 77:861-72. 2014
    ..Here we use lamivudine to show how a comprehensive population pharmacokinetic model can account for the influence of demographic covariates on exposure (i.e. AUC and Cmax )...
  62. ncbi request reprint Population pharmacokinetic-pharmacodynamic modelling of the anti-hyperalgesic effect of 5'deoxy-N6-cylopentyladenosine in the mononeuropathic rat
    Marloes P Schaddelee
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, PO Box 9502, 2300 RA Leiden, The Netherlands
    Eur J Pharmacol 504:7-15. 2004
    ..The high plasma concentrations required for the anti-hyperalgesic effect relative to the receptor affinity are consistent with restricted transport of 5'dCPA to the site of action in the spinal cord and/or the brain...
  63. ncbi request reprint Allometric scaling of pharmacodynamic responses: application to 5-Ht1A receptor mediated responses from rat to man
    Klaas P Zuideveld
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, P O Box 9502, 2300 RA, Leiden, The Netherlands
    Pharm Res 24:2031-9. 2007
    ..The aim of the present study was to assess whether two widely used biomarkers for 5-HT(1A)-receptor mediated responses in the rat (hypothermia and corticosterone increase) could be scaled to man using allometric principles...
  64. pmc Coping with time scales in disease systems analysis: application to bone remodeling
    Stephan Schmidt
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Einsteinweg 55, P O Box 9502, 2300RA, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 38:873-900. 2011
    ..It was also demonstrated how the simpler model could help in elucidating qualitative properties of the observed dynamics, such as the absence of overshoot and rebound, and the different dynamics of onset and washout...
  65. doi request reprint Application of a mechanism-based disease systems model for osteoporosis to clinical data
    Teun M Post
    Pharmacokinetics, Pharmacodynamics and Drug Metabolism PPDM, Merck Research Laboratories, Merck Sharp and Dohme, P O Box 20, 5340 BH, Oss, The Netherlands
    J Pharmacokinet Pharmacodyn 40:143-56. 2013
    ....
  66. doi request reprint A neonatal amikacin covariate model can be used to predict ontogeny of other drugs eliminated through glomerular filtration in neonates
    Roosmarijn F W De Cock
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Pharm Res 31:754-67. 2014
    ..The aim of this study was to evaluate whether this covariate model can be used to predict maturation in clearance of other renally excreted drugs...
  67. pmc The impact of P-gp functionality on non-steady state relationships between CSF and brain extracellular fluid
    Joost Westerhout
    Department of Pharmacology, Leiden Amsterdam Center for Drug Research, Einsteinweg 55, 2333 CC, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 40:327-42. 2013
    ..Therefore, information on functionality of P-gp is required for the prediction of human brain target site concentrations of P-gp substrates on the basis of human CSF concentrations...
  68. pmc Scaling of pharmacokinetics across paediatric populations: the lack of interpolative power of allometric models
    Massimo Cella
    LACDR, Division of Pharmacology, Leiden University, The Netherlands
    Br J Clin Pharmacol 74:525-35. 2012
    ..The objective of this investigation was to assess the performance of an allometric model as the basis for interpolating drug exposure in the context of pharmacokinetic bridging across paediatric subpopulations...
  69. pmc Physiologically based pharmacokinetic modeling to investigate regional brain distribution kinetics in rats
    Joost Westerhout
    Department of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    AAPS J 14:543-53. 2012
    ..The physiologically based pharmacokinetic modeling approach is important, as it allowed the prediction of human brain ECF exposure on the basis of human CSF concentrations...
  70. ncbi request reprint Pretreatment with a water-based surfactant formulation affects transdermal iontophoretic delivery of R-apomorphine in vitro
    Gai Ling Li
    Department of Pharmaceutical Technology, Leiden Amsterdam Centre for Drug Research, University of Leiden, PO Box 9502, 2300 RA, Leiden, The Netherlands
    Pharm Res 20:653-9. 2003
    ..To further increase the transdermal transport rate of R-apomorphine, a nonocclusive pretreatment with an aqueous surfactant formulation in combination with iontophoresis was explored in vitro...
  71. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling of 5-HT1A receptor agonists: estimation of in vivo affinity and intrinsic efficacy on body temperature in rats
    Klaas P Zuideveld
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden, The Netherlands
    J Pharmacol Exp Ther 308:1012-20. 2004
    ....
  72. ncbi request reprint Pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine and fentanyl in rats: role of receptor equilibration kinetics
    Ashraf Yassen
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, The Netherlands
    J Pharmacol Exp Ther 313:1136-49. 2005
    ..In contrast to earlier reports in the literature, the findings of this study show that the rate-limiting step in the onset and offset of buprenorphine's antinociceptive effect is distribution to the brain...
  73. ncbi request reprint Coupling of metal containing homing devices to liposomes via a maleimide linker: use of TCEP to stabilize thiol-groups without scavenging metals
    Corine C Visser
    Leiden Amsterdam Center for Drug Research LACDR, Leiden University, Division of Pharmacology, P O Box 9502, 2300 RA Leiden, The Netherlands
    J Drug Target 12:569-73. 2004
    ..This method can be applied to other metal-containing homing devices as well...
  74. ncbi request reprint Mechanism-based pharmacokinetic-pharmacodynamic modeling of the antinociceptive effect of buprenorphine in healthy volunteers
    Ashraf Yassen
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratories, The Netherlands
    Anesthesiology 104:1232-42. 2006
    ..The objective of this investigation was to characterize the pharmacokinetic-pharmacodynamic relation of buprenorphine's antinociceptive effect in healthy volunteers...
  75. pmc Systematic evaluation of the descriptive and predictive performance of paediatric morphine population models
    Elke H J Krekels
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Pharm Res 28:797-811. 2011
    ..One covariate model was based on a systematic covariate analysis, the other on fixed allometric scaling principles...
  76. pmc Identifying the translational gap in the evaluation of drug-induced QTc interval prolongation
    Anne S Y Chain
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Br J Clin Pharmacol 76:708-24. 2013
    ....
  77. pmc Developmental changes rather than repeated administration drive paracetamol glucuronidation in neonates and infants
    Elke H J Krekels
    Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden, The Netherlands
    Eur J Clin Pharmacol 71:1075-82. 2015
    ..This study investigates paracetamol clearance in neonates and infants after single and multiple dosing using a population modelling approach...
  78. pmc A model-based approach for the evaluation of once daily dosing of lamivudine in HIV-infected children
    Chiara Piana
    LACDR, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Br J Clin Pharmacol 77:852-60. 2014
    ..Here we investigate whether a once daily dosing regimen of lamivudine provides comparable exposure to the currently approved paediatric regimen...
  79. doi request reprint Population pharmacokinetics of paracetamol across the human age-range from (pre)term neonates, infants, children to adults
    Chenguang Wang
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands Erasmus MC Sophia Children s Hospital, Intensive Care and Department of Paediatric Intensive Care, Rotterdam, The Netherlands
    J Clin Pharmacol 54:619-29. 2014
    ..Clearance was found to change in a nonlinear manner with bodyweight. Based on the final model, dosing guidelines are proposed from preterm neonates to adolescents resulting in similar exposure across all age ranges. ..
  80. pmc Population pharmacokinetic model of the pregabalin-sildenafil interaction in rats: application of simulation to preclinical PK-PD study design
    Gregor Bender
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden University, Leiden, The Netherlands
    Pharm Res 26:2259-69. 2009
    ..The focus of this study was to determine the influence of sildenafil on the pharmacokinetics (PK) of pregabalin with the objective of informing the design of a quantitative pharmacodynamic (PD) study...
  81. doi request reprint Low but inducible contribution of renal elimination to clearance of propylene glycol in preterm and term neonates
    Roosmarijn F W De Cock
    Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands Neonatal Intensive Care Unit Centre for Clinical Pharmacology, University Hospitals Leuven, Leuven, Belgium and Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands
    Ther Drug Monit 36:278-87. 2014
    ..The aim of this study is to characterize the renal and hepatic elimination of PG in preterm and term neonates...
  82. doi request reprint Evidence-based morphine dosing for postoperative neonates and infants
    Elke H J Krekels
    Division of Pharmacology, Leiden Academic Center for Drug Research, Leiden University, Leiden, The Netherlands
    Clin Pharmacokinet 53:553-63. 2014
    ..Compared with traditional dosing, this model-derived dosing regimen yields significantly reduced doses in neonates aged <10 days...
  83. pmc The allometric exponent for scaling clearance varies with age: a study on seven propofol datasets ranging from preterm neonates to adults
    Chenguang Wang
    Division of Pharmacology, LACDR, Leiden University, Leiden, the Netherlands Intensive Care and Department of Paediatric Intensive Care, Erasmus MC Sophia Children s Hospital, Rotterdam, The Netherlands
    Br J Clin Pharmacol 77:149-59. 2014
    ..75 is often applied. In this analysis, we performed a systematic study on the allometric exponent for scaling propofol clearance between two subpopulations selected from neonates, infants, toddlers, children, adolescents and adults...
  84. pmc Developmental pharmacokinetics of propylene glycol in preterm and term neonates
    Roosmarijn F W De Cock
    Division of Pharmacology, LACDR, Leiden University, Leiden, The Netherlands
    Br J Clin Pharmacol 75:162-71. 2013
    ....
  85. doi request reprint Prediction of morphine clearance in the paediatric population : how accurate are the available pharmacokinetic models?
    Elke H J Krekels
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Clin Pharmacokinet 51:695-709. 2012
    ....
  86. pmc A new minimal-stress freely-moving rat model for preclinical studies on intranasal administration of CNS drugs
    Jasper Stevens
    Division of Pharmacology, LACDR Leiden University, Leiden, The Netherlands
    Pharm Res 26:1911-7. 2009
    ..To develop a new minimal-stress model for intranasal administration in freely moving rats and to evaluate in this model the brain distribution of acetaminophen following intranasal versus intravenous administration...
  87. ncbi request reprint Transdermal iontophoresis of rotigotine: influence of concentration, temperature and current density in human skin in vitro
    Akhmad Kharis Nugroho
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, University of Leiden, P O Box 9502, Einsteinweg 55, 2300 RA Leiden, The Netherlands
    J Control Release 96:159-67. 2004
    ..The maximum Flux(ss) achieved was around 80 nmol cm(-2) h(-1) indicating that by means of iontophoresis, a therapeutic level of rotigotine might be achieved with a reasonable patch size...
  88. ncbi request reprint Characterization and modulation of the transferrin receptor on brain capillary endothelial cells
    Corine C Visser
    Leiden Amsterdam Center for Drug Research LACDR, Leiden University, Division of Pharmacology, 2300 RA Leiden, The Netherlands
    Pharm Res 21:761-9. 2004
    ....
  89. ncbi request reprint Compartmental modeling of transdermal iontophoretic transport II: in vivo model derivation and application
    Akhmad Kharis Nugroho
    Division of Drug Delivery Technology, Leiden Amsterdam Center for Drug Research, 2300 RA Leiden, The Netherlands
    Pharm Res 22:335-46. 2005
    ..The new models are based on previously proposed compartmental models for the transport in vitro...
  90. doi request reprint Sensitivity of the individual items of the Hamilton depression rating scale to response and its consequences for the assessment of efficacy
    Gijs Santen
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, P O Box 9502, Leiden, The Netherlands
    J Psychiatr Res 42:1000-9. 2008
    ..This response-based subscale increases signal-to-noise ratio and could reduce failure rate in efficacy trials with antidepressant drugs...
  91. doi request reprint The missing link between clinical endpoints and drug targets in depression
    Oscar Della Pasqua
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Trends Pharmacol Sci 31:144-52. 2010
    ..A mechanism-based approach accounting for the multidimensional nature of symptoms and signs is required. Composite endpoints that reflect the underlying mechanisms of action need to be developed without further ado...
  92. pmc The role of population PK-PD modelling in paediatric clinical research
    Roosmarijn F W De Cock
    Division of Pharmacology, Leiden Amsterdam Centre for Drug Research, Leiden University, Leiden, The Netherlands
    Eur J Clin Pharmacol 67:5-16. 2011
    ..This methodology will improve the efficacy/safety balance of dosing guidelines, which will be of benefit to the individual child...
  93. doi request reprint Advances in paediatric pharmacokinetics
    Catherijne A J Knibbe
    University of Leiden, Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Leiden, The Netherlands
    Expert Opin Drug Metab Toxicol 7:1-8. 2011
    ..Even though pharmacokinetic and pharmacodynamic relations determine together the optimal drug dose, age-related changes in pharmacokinetics have proven of utmost importance for optimising drug dosing in children...
  94. doi request reprint Predictive performance of a recently developed population pharmacokinetic model for morphine and its metabolites in new datasets of (preterm) neonates, infants and children
    Elke H J Krekels
    Division of Pharmacology, LeidenAmsterdam Center for Drug Research, Leiden, The Netherlands
    Clin Pharmacokinet 50:51-63. 2011
    ....
  95. ncbi request reprint Ontogeny of hepatic glucuronidation; methods and results
    Elke H J Krekels
    Division of Pharmacology, Leiden Amsterdam Center for Drug Research, Leiden, The Netherlands
    Curr Drug Metab 13:728-43. 2012
    ....
  96. ncbi request reprint Pharmacodynamic analysis of the interaction between tiagabine and midazolam with an allosteric model that incorporates signal transduction
    Daniël M Jonker
    Leiden Amsterdam Center for Drug Research, Division of Pharmacology, Gorlaeus Laboratory, Leiden, The Netherlands
    Epilepsia 44:329-38. 2003
    ....
  97. ncbi request reprint Population pharmacokinetic analysis for simultaneous determination of B (max) and K (D) in vivo by positron emission tomography
    Lia C Liefaard
    Division of Pharmacology, LACDR, Leiden University, P O Box 9502, 2300 RA, Leiden, The Netherlands
    Mol Imaging Biol 7:411-21. 2005
    ..A novel approach, using positron emission tomography (PET) and [C-11]flumazenil ([C-11]FMZ), was developed for simultaneous estimation of GABA(A)-receptor properties, characterized by B (max) and K (D)...
  98. doi request reprint Online solid phase extraction with liquid chromatography-tandem mass spectrometry to analyze remoxipride in small plasma-, brain homogenate-, and brain microdialysate samples
    Jasper Stevens
    Division of Pharmacology, LACDR Leiden University, Leiden, The Netherlands
    J Chromatogr B Analyt Technol Biomed Life Sci 878:969-75. 2010
    ..Considering the small sample volumes, the high sensitivity and good reproducibility, the analytical methods are suitable for analyzing small sample volumes with low remoxipride concentrations...
  99. ncbi request reprint A mechanism-based disease progression model for comparison of long-term effects of pioglitazone, metformin and gliclazide on disease processes underlying Type 2 Diabetes Mellitus
    Willem de Winter
    LAP and P Consultants BV, Leiden, The Netherlands
    J Pharmacokinet Pharmacodyn 33:313-43. 2006
    ....
  100. ncbi request reprint Reproducible and time-dependent modification of serum protein binding in Wistar Kyoto rats
    Tamara J van Steeg
    Leiden Amsterdam Center for Drug Research, Leiden University, Division of Pharmacology, Leiden, The Netherlands
    J Pharmacol Toxicol Methods 56:72-8. 2007
    ..Here we present an experimental approach to modify serum protein levels and binding in the rat, in a robust, reproducible, and time-dependent manner...
  101. doi request reprint Explaining variability in tacrolimus pharmacokinetics to optimize early exposure in adult kidney transplant recipients
    Rogier R Press
    Department of Clinical Pharmacy and Toxicology, Leiden University Medical Center, Albinusdreef 2, Leiden, The Netherlands
    Ther Drug Monit 31:187-97. 2009
    ..5 times higher, fixed, starting dose compared with CYP3A5*3/*3 to reach the predefined target exposure early after transplantation...