A5049073682- Antibiotics Pharmacokinetics and Efficacy
- Drug Transport and Resistance Mechanisms
- Antibiotic Resistance in Bacteria
- Computational Drug Discovery Methods
- Pneumonia and Respiratory Infections
- Statistical Methods in Clinical Trials
- Cannabis and Cannabinoid Research
- Pharmacogenetics and Drug Metabolism
- Epilepsy research and treatment
- Evolution and Genetic Dynamics
- Psychedelics and Drug Studies
- Antimicrobial Resistance in Staphylococcus
- Cancer Treatment and Pharmacology
- Bioinformatics and Genomic Networks
- Pharmacological Effects and Toxicity Studies
- Tuberculosis Research and Epidemiology
- Cancer Genomics and Diagnostics
- Gene Regulatory Network Analysis
- Forensic Toxicology and Drug Analysis
- Metabolomics and Mass Spectrometry Studies
- Chemotherapy-induced cardiotoxicity and mitigation
- Sepsis Diagnosis and Treatment
- Immune Response and Inflammation
- Economic and Financial Impacts of Cancer
- Health Systems, Economic Evaluations, Quality of Life
Centre for Human Drug Research
2016-2025
Leiden University
2016-2025
Icahn School of Medicine at Mount Sinai
2016-2021
The Netherlands Cancer Institute
2011-2019
Center for Systems Biology
2018
Pharmac
2018
Oncode Institute
2011-2016
Slotervaartziekenhuis
2011-2015
Dutch Cancer Society
2013
GlaxoSmithKline (Netherlands)
2013
This article represents the first in a series of tutorials on model evaluation nonlinear mixed effect models (NLMEMs), from International Society Pharmacometrics (ISoP) Model Evaluation Group. Numerous tools are available for NLMEM, with particular emphasis visual assessment. basic tutorial focuses presenting graphical NLMEM continuous data. It illustrates graphs correct or misspecified models, discusses their pros and cons, recalls definition metrics used.
While it is known that endocannabinoids (eCB) modulate multiple neuronal functions, the molecular mechanism governing their release and transport remains elusive. Here, we propose an "on-demand release" model, wherein formation of microvesicles, a specific group extracellular vesicles (EVs) containing eCB, 2-arachidonoylglycerol (2-AG), important step. A coculture model system combines reporter cell line expressing fluorescent eCB sensor, G protein-coupled receptor-based (GRAB)eCB2.0, cells...
Sepsis is a major contributor to neonatal mortality, particularly in low-income and middle-income countries (LMICs). WHO advocates ampicillin-gentamicin as first-line therapy for the management of sepsis. In BARNARDS observational cohort study sepsis antimicrobial resistance LMICs, common pathogens were characterised via whole genome sequencing (WGS) profiles. this substudy BARNARDS, we aimed assess use efficacy empirical antibiotic therapies commonly used LMICs
In the POET (Partial Oral Endocarditis Treatment) trial, oral step-down therapy was noninferior to full-length intravenous antibiotic administration. The aim of present study perform pharmacokinetic/pharmacodynamic analyses for treatments infective endocarditis assess probabilities target attainment (PTAs).Plasma concentrations antibiotics were measured at day 1 and 5. Minimal inhibitory (MICs) determined bacteria causing (streptococci, staphylococci, or enterococci)....
Abstract The evolution of antimicrobial resistance (AMR) in biofilms has been repeatedly studied by experimental vitro, but rarely vivo. complex microenvironment at the infection site imposes selective pressures on bacterial biofilms, potentially influencing development AMR. We report here AMR an vivo mouse model Pseudomonas aeruginosa biofilm lung infection. P. embedded seaweed alginate beads underwent four successive passages with or without ciprofloxacin (CIP) exposure. CIP was assessed...
3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert–Eaton myasthenic syndrome (LEMS), either alone or in combination. enhances the release of acetylcholine at neuromuscular synapse, inhibits degradation this neurotransmitter. Although could lead a synergistic effect on transmission, no studies have compared effects these drugs patients with LEMS. Therefore, we performed placebo-controlled, double-dummy, double-blind, randomized, crossover study nine Clinical Pharmacology...
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...
Creating a cDNA library for deep mRNA sequencing (mRNAseq) is generally done by random priming, creating multiple fragments along each transcript. A 3'-end-focused approach cannot detect differential splicing, but has potentially higher throughput at lower cost, with the ability to improve quantification using transcript molecule counting unique molecular identifiers (UMI) that correct PCR bias. Here, we compare an implementation of such 3'-digital gene expression (3'-DGE) "conventional"...
Predicting target site drug concentration in the brain is of key importance for successful development drugs acting on central nervous system. We propose a generic mathematical model to describe pharmacokinetics compartments, and apply this predict human disposition. A consisting several physiological compartments rat was developed using rich concentration-time profiles from nine structurally diverse plasma, extracellular fluid, two cerebrospinal fluid compartments. The effect active...
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Cannabis based medicines are registered as a treatment for various indications, such pain and spasms in multiple sclerosis (MS) patients, anorexia nausea patients with HIV or receiving cancer treatment. the pharmacokinetics of administration routes cannabis variable dosing is hard to regulate. STUDY ADDS Namisol new tablet containing pure THC (>98%) that has beneficial pharmacokinetic profile after oral administration. gives quick onset...
ABSTRACT The present study determined the pharmacokinetic profile of vancomycin in premature Malaysian infants. A one-compartment infusion model with first-order elimination was fitted to serum concentration data ( n = 835 points) obtained retrospectively from drug monitoring records 116 newborn Vancomycin concentrations were estimated by a fluorescence polarization immunoassay. Population and individual estimates clearance distribution volume factors which affected variability observed for...
Abstract Aims The enzymatic activity of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) are important for the tolerability efficacy fluoropyrimidine drugs. In present study, we explored between‐subject variability (BSV) circadian rhythmicity in DPD TS human volunteers. Methods BSVs ( n = 20) peripheral blood mononuclear cells (PBMCs) plasma, measured by means dihydrouracil (DHU) uracil (U) plasma levels DHU : U ratio 40), PBMCs 19), were examined. Samples collected every...
Collateral sensitivity (CS)-based antibiotic treatments, where increased resistance to one leads a second antibiotic, may have the potential limit emergence of antimicrobial resistance. However, it remains unclear how best design CS-based treatment schedules. To address this problem, we use mathematical modelling study effects pathogen- and drug-specific characteristics for different designs on bacterial population dynamics evolution. We confirm that simultaneous one-day cycling treatments...