A5037422391- Chronic Myeloid Leukemia Treatments
- Chronic Lymphocytic Leukemia Research
- Cancer Treatment and Pharmacology
- Pancreatic and Hepatic Oncology Research
- Pharmacogenetics and Drug Metabolism
- Antibiotics Pharmacokinetics and Efficacy
- PI3K/AKT/mTOR signaling in cancer
- Colorectal Cancer Treatments and Studies
- Immunodeficiency and Autoimmune Disorders
- Lung Cancer Treatments and Mutations
- Monoclonal and Polyclonal Antibodies Research
- Drug Transport and Resistance Mechanisms
- Lymphoma Diagnosis and Treatment
- Genetic diversity and population structure
- Ion channel regulation and function
- Cardiac electrophysiology and arrhythmias
- HER2/EGFR in Cancer Research
- Genetic and phenotypic traits in livestock
- Polyamine Metabolism and Applications
- Amino Acid Enzymes and Metabolism
- Multiple Myeloma Research and Treatments
- Advancements in Transdermal Drug Delivery
- Radiopharmaceutical Chemistry and Applications
- Radiomics and Machine Learning in Medical Imaging
- T-cell and B-cell Immunology
China Medical University
2021-2024
The Netherlands Cancer Institute
2013-2022
Novartis (Switzerland)
2019-2022
University of Florida
2020
Columbus Oncology and Hematology Associates
2020
Great Ormond Street Hospital
2018-2019
University College London
2018-2019
Leiden University
2013-2018
Centre for Human Drug Research
2013-2018
Slotervaartziekenhuis
2013-2016
The cellular polyamines spermine, spermidine, and their metabolic precursor putrescine, have long been associated with cell-growth, tumor-related gene regulations, Alzheimer's disease. Here, we show by in vitro spectroscopy AFM imaging, that these molecules promote aggregation of amyloid-beta (Aβ) peptides into fibrils modulate the pathways. NMR measurements showed three share a similar binding mode to monomeric Aβ(1-40) peptide. Kinetic ThT studies already very low polyamine concentrations...
Interpatient variability in the pharmacokinetics (PK) of sunitinib is high. Single nucleotide polymorphisms (SNPs) PK candidate genes have been associated with efficacy and toxicity sunitinib, but whether these SNPs truly affect remains to be elucidated. This multicenter study involving 114 patients investigated haplotypes encoding metabolizing enzymes or efflux transporters are clearance its active metabolite SU12662. were tested as covariates a population model. From univariate analysis,...
Ofatumumab, a fully human anti-CD20 monoclonal antibody indicated for the treatment of relapsing forms multiple sclerosis (RMS), binds to unique conformational epitope, thereby depleting B cells very efficiently and allowing subcutaneous administration at lower doses. The aims were characterize relationship between ofatumumab concentration cell levels, including effect covariates such as body weight, age, or baseline count, use simulations confirm chosen therapeutic dose. Graphical...
The aim of this work was to develop a nanolayered pH sensitive coating method whereby proteins are coated at suitable on the surface chemically modified biomedical/bioanalytical microdevices and protein release is triggered by pH-shift upon contact with physiological environment. In such developed applied onto microneedles. First, microneedle arrays basic groups pKa below pH. This modification multistep procedure: first hydroxylated in piranha mixture, then 3-aminopropyl-triethoxysilane...
To predict first‐pass and systemic cytochrome P450 (CYP) 3A‐mediated metabolism of midazolam in preterm neonates, a physiological population pharmacokinetic model was developed describing intestinal hepatic clearance infants. On the basis 1‐OH‐midazolam concentrations from 37 neonates (gestational age 26–34 weeks) receiving orally and/or via 30‐minute intravenous infusion, intrinsic gut wall liver were found to be very low, with lower values (0.0196 6.7 L/h, respectively). This results...
Previously published pharmacokinetic (PK) models for sunitinib and its active metabolite SU12662 were based on a limited dataset or lacked important elements such as correlations between metabolite. The current study aimed to develop an improved PK model that circumvented these limitations prove the utility of in treatment optimization clinical practice.One thousand two hundred five plasma samples from 70 cancer patients collected three studies with SU12662. A semi-physiological was...
Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal hepatic CYP3A-mediated of midazolam children order predict systemic CYP3A substrates.Pharmacokinetic (PK) data 1-OH-midazolam from 264 post-operative 1-18 years after oral administration were analyzed using a physiological population PK modelling approach. In model, consisting compartments representing gastro-intestinal tract liver,intrinsic...
As pazopanib plasma trough concentrations are correlated with treatment outcome, we explored whether single nucleotide polymorphisms in the elimination pathway of affect systemic concentrations. The decreased function alleles CYP3A4 15389 C > T (*22), ABCB1 3435 >T, ABCG2 421 >A, and 34G >A were analyzed within a recently developed population-pharmacokinetic model. Incorporation CYP3A4*22 model resulted 35% lower clearance for variant carriers (0.18 vs. 0.27 L/h; difference objective value:...
For scaling drug plasma clearance (CLp) from adults to children, extrapolations of population pharmacokinetic (PopPK) covariate models between drugs sharing an elimination pathway have enabled accelerated development pediatric and dosing recommendations. This study aims at identifying conditions for which this approach consistently leads accurate specific CLp children undergoing hepatic metabolism. A physiologically based (PBPK) simulation workflow utilizing mechanistic equations defining...
Abstract Oral administration of docetaxel is an attractive alternative for conventional intravenous (IV) administration. The low bioavailability docetaxel, however, hinders the application oral in clinic. aim current study was to develop a population pharmacokinetic (PK) model and ritonavir based on phase 1 studies support drug development this combination treatment. PK data were collected from 191 patients who received IV different formulations (drinking solution, ModraDoc001 capsule,...
Current studies lack a comprehensive understanding of the environmental factors influencing type 2 diabetes, hindering an in-depth grasp overall etiology. To address this gap, we utilized network science tools to highlight research trends, knowledge structures, and intricate relationships among factors, offering new perspective for profound
Aims Rituximab is a chimeric IgG‐1 monoclonal antibody that depletes B cells, aiding in the treatment of several conditions including autoimmune diseases. It not licensed for use children. This study aimed to quantify cell‐related pharmacodynamics rituximab children with disease. Methods Routine electronic health record data were collected at large paediatric tertiary hospital London, UK. Dosing protocols either 2 × 750 mg/m intravenous infusions on days 1 and 15, or 4 375 1, 8, 15 22....
Significant differences between dogs and humans have been observed in the concentration-QTc effect relationship of compounds with known pro-arrhythmic properties. These findings suggest that interspecies must be considered when evaluating drug effects. The aim this study was to evaluate performance a model-based approach assess risk QTc prolongation for three investigational (NCE01, NCE02 NCE03).Pharmacokinetic pharmacodynamic data from experiments conscious healthy subjects were included...
In spite of screening procedures in early drug development, uncertainty remains about the propensity new chemical entities (NCEs) to prolong QT/QTc interval. The evaluation proarrhythmic activity using a comprehensive vitro proarrhythmia assay does not fully account for pharmacokinetic-pharmacodynamic (PKPD) differences vivo. present study, we evaluated correlation between drug-specific parameters describing QT interval prolongation dogs and humans.