25 Result(s)

Article

A New Minimal-Stress Freely-Moving Rat Model for Preclinical Studies on Intranasal Administration of CNS Drugs

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 administrati...

Jasper Stevens, Ernst Suidgeest, Piet Hein van der Graaf… in Pharmaceutical Research (2009)

Article

Physiologically Based Pharmacokinetic Modeling to Investigate Regional Brain Distribution Kinetics in Rats

One of the major challenges in the development of central nervous system (CNS)-targeted drugs is predicting CNS exposure in human from preclinical data. In this study, we present a methodology to investigate b...

Joost Westerhout, Bart Ploeger, Jean Smeets, Meindert Danhof… in The AAPS Journal (2012)

Article

Utility of CSF in translational neuroscience

Human cerebrospinal fluid (CSF) sampling is of high value as the only general applicable methodology to obtain information on free drug concentrations in individual human brain. As the ultimate interest is in ...

Elizabeth C. M. de Lange in Journal of Pharmacokinetics and Pharmacodynamics (2013)

Article

The impact of P-gp functionality on non-steady state relationships between CSF and brain extracellular fluid

In the development of central nervous system (CNS)-targeted drugs, the prediction of human CNS target exposure is a big challenge. Cerebrospinal fluid (CSF) concentrations have often been suggested as a ‘good ...

Joost Westerhout, Jean Smeets… in Journal of Pharmacokinetics and Pharmacody… (2013)

Article

Diurnal Variation in P-glycoprotein-Mediated Transport and Cerebrospinal Fluid Turnover in the Brain

Nearly all bodily processes exhibit circadian rhythmicity. As a consequence, the pharmacokinetic and pharmacodynamic properties of a drug may also vary with time of day. The objective of this study was to inve...

Laura Kervezee, Robin Hartman, Dirk-Jan van den Berg, Shinji Shimizu… in The AAPS Journal (2014)

Article

Emerging Insights for Translational Pharmacokinetic and Pharmacokinetic-Pharmacodynamic Studies: Towards Prediction of Nose-to-Brain Transport in Humans

To investigate the potential added value of intranasal drug administration, preclinical studies to date have typically used the area under the curve (AUC) in brain tissue or cerebrospinal fluid (CSF) compared ...

Mitchel J. R. Ruigrok, Elizabeth C. M. de Lange in The AAPS Journal (2015)

Article

A Generic Multi-Compartmental CNS Distribution Model Structure for 9 Drugs Allows Prediction of Human Brain Target Site Concentrations

Predicting target site drug concentration in the brain is of key importance for the successful development of drugs acting on the central nervous system. We propose a generic mathematical model to describe the...

Yumi Yamamoto, Pyry A. Välitalo, Dirk-Jan van den Berg… in Pharmaceutical Research (2017)

Article

Erratum to: Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations

Yumi Yamamoto, Meindert Danhof, Elizabeth C. M. de Lange in The AAPS Journal (2017)

Article

Microdialysis: the Key to Physiologically Based Model Prediction of Human CNS Target Site Concentrations

Despite the enormous research efforts that have been put into the development of central nervous system (CNS) drugs, the success rate in this area is still disappointing. To increase the successful rate in the...

Yumi Yamamoto, Meindert Danhof, Elizabeth C. M. de Lange in The AAPS Journal (2017)

Article

Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling

Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of ...

Anna H. C. Vlot, Wilhelmus E. A. de Witte, Meindert Danhof… in The AAPS Journal (2017)

Article

Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models

Drug–target binding kinetics (as determined by association and dissociation rate constants, k_on and k_off) can be an important determinant of the kinetics of drug action. However, the effect compartment model is u...

Wilhelmus E. A. de Witte, Vivi Rottschäfer… in Journal of Pharmacokinetics and Pharmacody… (2018)

Article

Correction to: Modelling the delay between pharmacokinetics and EEG effects of morphine in rats: binding kinetic versus effect compartment models

The original version of this article was published open access. Unfortunately, due to a technical issue, the copyright holder name in the online version (HTML and XML) is incorrectly published as “Springer Sci...

Wilhelmus E. A. de Witte, Vivi Rottschäfer… in Journal of Pharmacokinetics and Pharmacody… (2018)

Article

The 3D Brain Unit Network Model to Study Spatial Brain Drug Exposure under Healthy and Pathological Conditions

We have developed a 3D brain unit network model to understand the spatial-temporal distribution of a drug within the brain under different (normal and disease) conditions. Our main aim is to study the impact o...

Esmée Vendel, Vivi Rottschäfer, Elizabeth C.M. de Lange in Pharmaceutical Research (2020)

Article

Lumbar cerebrospinal fluid-to-brain extracellular fluid surrogacy is context-specific: insights from LeiCNS-PK3.0 simulations

Predicting brain pharmacokinetics is critical for central nervous system (CNS) drug development yet difficult due to ethical restrictions of human brain sampling. CNS pharmacokinetic (PK) profiles are often al...

Mohammed A. A. Saleh, Chi Fong Loo… in Journal of Pharmacokinetics and Pharmacody… (2021)