A5017208135- Drug Transport and Resistance Mechanisms
- Pharmacological Effects and Toxicity Studies
- Epilepsy research and treatment
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Antibiotics Pharmacokinetics and Efficacy
- Pharmacogenetics and Drug Metabolism
- Barrier Structure and Function Studies
- Computational Drug Discovery Methods
- Neurotransmitter Receptor Influence on Behavior
- Nanoparticle-Based Drug Delivery
- Alzheimer's disease research and treatments
- Neuropeptides and Animal Physiology
- Hypothalamic control of reproductive hormones
- Pregnancy and Medication Impact
- Protein Interaction Studies and Fluorescence Analysis
- Glioma Diagnosis and Treatment
- Traumatic Brain Injury and Neurovascular Disturbances
- Schizophrenia research and treatment
- Metabolomics and Mass Spectrometry Studies
- Metabolism and Genetic Disorders
- Diet and metabolism studies
- Lipid Membrane Structure and Behavior
- Advanced Drug Delivery Systems
- Dementia and Cognitive Impairment Research
Leiden University
2016-2025
Centre for Human Drug Research
2016-2025
University of Applied Sciences Mainz
2009
Wolters Kluwer (Netherlands)
2008
RWTH Aachen University
2008
Leiden University Medical Center
2001-2002
Maastricht University
2001
Multidrug resistance protein 1 (MRP1) is a transporter that helps to protect normal cells and tumor against the influx of certain xenobiotics. We previously showed Mrp1 protects cytotoxic drugs at testis-blood barrier, oral epithelium, kidney urinary collecting duct tubules. Here, we generated Mrp1/Mdr1a/Mdr1b triple-knockout (TKO) mice, used them together with Mdr1a/Mdr1b double-knockout (DKO) mice study contribution tissue distribution pharmacokinetics etoposide. observed increased...
Abstract Mice with a genetic disruption of the multiple drug resistance (mdr1a) gene were used to examine effect absence its drug-transporting P-glycoprotein product from blood-brain barrier on distribution and cell nuclear uptake of[ 3H]-dexamethasone in brain.[ (4 μg/kg mouse) was administered sc adrenalectomized mdr1a (−/−) (+/+) mice. One hour later, mice decapitated, radioactivity measured homogenates cerebellum, blood, liver following extraction radioactive steroid. The frontal brain...
In the present study, we investigated role of multidrug resistance (mdr) P-glycoprotein (Pgp) at blood-brain barrier in control access cortisol and corticosterone to mouse human brain. [3H]Cortisol poorly penetrated brain adrenalectomized wild-type mice, but uptake was 3.5-fold enhanced after disruption Pgp expression mdr 1a−/− mice. sharp contrast, treatment with [3H]corticosterone revealed high labeling tissue without difference between both genotypes. Interestingly, MDR1 also...
The aim of this study was to investigate whether blood‐brain barrier transport morphine affected by the absence mdr1a ‐encoded P‐glycoprotein (Pgp), comparing (−/−) mice with (+/+) mice. Mdr1a and received a constant infusion for 1, 2 or 4 h (9 nmol/min/mouse). Microdialysis used estimate unbound concentrations in brain extracellular fluid during infusion. Two methods estimating vivo recovery were used: retrodialysis nalorphine as calibrator, dynamic‐no‐net‐flux method. Retrodialysis loss...
Partly due to poor blood–brain barrier drug penetration the treatment options for many brain diseases are limited. To safely enhance delivery brain, glutathione PEGylated liposomes (G-Technology®) were developed. In this study, in rats, we compared pharmacokinetics and organ distribution of GSH-PEG using an autoquenched fluorescent tracer after intraperitoneal administration intravenous administration. Although appearance circulation was much slower administration, comparable maximum levels...
Despite enormous advances in CNS research, disorders remain the world's leading cause of disability. This accounts for more hospitalizations and prolonged care than almost all other diseases combined, indicates a high unmet need good drugs drug therapies.Following dosing, not only chemical properties blood-brain barrier (BBB) transport, but also many processes will ultimately determine brain target site kinetics consequently effects. The rate extent these are regulated dynamically, thus...
Drug development targeting the central nervous system (CNS) is challenging due to poor predictability of drug concentrations in various CNS compartments. We developed a generic physiologically based pharmacokinetic (PBPK) model for prediction relevant System-specific and drug-specific parameters were derived from literature silico predictions. The was validated using detailed concentration-time profiles 10 drugs rat plasma, brain extracellular fluid, 2 cerebrospinal fluid sites, total...