Publications related to Physiologically based pharmacokinetic modelling

Molecular analysis and therapeutic applications of human serum albumin-fatty acid interactions

Alessandro Angelini, Alessandro Zorzi, Sara Linciano

Human serum albumin (hSA) is the major carrier protein for fatty acids (FAs) in plasma. Its ability to bind multiple FA moieties with moderate to high affinity has inspired the use of FA conjugation as a safe and natural platform to generate long-lasting t ...

ELSEVIER2022

Determination of a clinically effective evobrutinib dose: Exposure-response analyses of a phase II relapsing multiple sclerosis study

Mitchell David Anderson

The pharmacometric analysis of the double-blind, randomized, phase II study (NCT02975349) investigating the safety and efficacy of evobrutinib, explored exposure-response relationships and suitable dosing regimens of evobrutinib for relapsing multiple scle ...

WILEY2022

Development of Tissue Kallikrein Inhibitors for the Treatment of Netherton Syndrome

Patrick Andreas Gonschorek

There is currently no approved treatment for Netherton syndrome, which is a severe, genetic skin disease characterized by chronic inflammation and excessive peeling of the skin. Even though the molecular disease mechanism has been assigned to the unopposed ...

EPFL2019

Gut microbial transformation of the dietary mutagen MeIQx may reduce exposure levels without altering intestinal transport

Julita Maria Stadnicka-Michalak, Jianbo Zhang

The mutagen and probable human carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) is metabolized in the colon to 9-hydroxyl-2,7-dimethyl-7,9,10,11-tetrahydropyrimido[2',1':2,3]imidazo[4,5-f]quinoxaline (MeIQx-M1) by conjugation with microbial ...

PERGAMON-ELSEVIER SCIENCE LTD2019

Gender medicine and oncology: report and consensus of an ESMO workshop

Jacques Fellay

Background: The importance of sex and gender as modulators of disease biology and treatment outcomes is well known in other disciplines of medicine, such as cardiology, but remains an undervalued issue in oncology. Considering the increasing evidence for t ...

OXFORD UNIV PRESS2019

Generating Safety Guidance for Medical Injection with Three-Compartment Pharmacokinetics Model

Giovanni De Micheli, Francesca Stradolini, Heinz Riener, Cunxi Yu

Medical cyber-physical systems are a new trend of software controlled physical systems that are increasingly common in medical domains. With rapid developments in medical science and computer technology, safety verification and simulation becomes more chal ...

IEEE2018

Single-cell division and killing dynamics of bacteria exposed to isocratic and time-dependent concentrations of antibiotic

Katrin Esther Schneider

Antibiotic resistance, defined as the ability of a bacteria to survive an antibiotic drug to which it was initially sensitive, has become increasingly worrying. While the discovery of antibiotics is considered to be one of the most important of all biomedi ...

EPFL2018

Intra- and extra-axonal axial diffusivities in the white matter: Which one is faster?

Ileana Ozana Jelescu, Nicolas Kunz

A two-compartment model of diffusion in white matter, which accounts for intra- and extra-axonal spaces, is associated with two plausible mathematical scenarios: either the intra-axonal axial diffusivity Da,‖ is higher than the extra-axonal De,‖ (Branch 1) ...

2018

Development of an albumin-binding ligand for prolonging the plasma half-life of peptide therapeutics

Alessandro Zorzi

Peptides represent a promising format for the development of therapeutics since they combine the advantages of proteins and small molecules. Several techniques based on rational design or in vitro evolution can be used to develop peptides as therapeutics. ...

EPFL2017

Progress towards in vivo brain (13)C-MRS in mice: Metabolic flux analysis in small tissue volumes

Rolf Gruetter, Bernard Lanz, Marta Lai

The combination of dynamic (13)C MRS data under infusion of (13)C-labeled substrates and compartmental models of cerebral metabolism enabled in vivo measurement of metabolic fluxes with a quantitative and distinct determination of cellular-specific activit ...

Elsevier2017

Antihypertensive drugs metabolism: an update to pharmacokinetic profiles and computational approaches

Vassily Hatzimanikatis, Ljubisa Miskovic, Aikaterini Zisaki

Drug discovery and development is a high-risk enterprise that requires significant investments in capital, time and scientific expertise. The studies of xenobiotic metabolism remain as one of the main topics in the research and development of drugs, cosmet ...

Bentham Science Publishers2015

Study of the influence of over-the-counter vitamin supplement intake on urine fluorescence to optimize cancer detection by fluorescence cystoscopy

Hubert van den Bergh, Georges Wagnières, Matthieu Philippe Emmanuel Zellweger, Carla Martoccia

Fluorescence cystoscopy (FC) efficiently enhances the detection and improves the therapeutic management of early bladder cancer. During an FC, about 150 ml of water is needed to inflate the bladder. The water is quickly diluted by urine which can be fluore ...

SPIE Society of Photo-optical Instrumentation Engineers2015

Measured and Modeled Toxicokinetics in Cultured Fish Cells and Application to In Vitro - In Vivo Toxicity Extrapolation

Kristin Schirmer, Julita Maria Stadnicka-Michalak

Effect concentrations in the toxicity assessment of chemicals with fish and fish cells are generally based on external exposure concentrations. External concentrations as dose metrics, may, however, hamper interpretation and extrapolation of toxicological ...

Public Library Science2014

Directed Evolution of Bicyclic Peptides for Therapeutic Application

Christian Heinis, Philippe Diderich

Many naturally occurring cyclic peptides or derivatives thereof are used as therapeutics such as the human hormones vasopressin and oxytocin or the antibiotics vancomycin and daptomycin. The success of cyclic peptide therapeutics is based on their ability ...

Schweizerische Chemische Gesellschaft2013

Brain Glucose Transport and Phosphorylation Under Acute Insulin-Induced Hypoglycemia in Mice: An 18F-FDG PET Study

Rolf Gruetter, João Miguel das Neves Duarte, Malte Alf

We addressed the questions of how cerebral glucose transport and phosphorylation change under acute hypoglycemia and what the underlying mechanisms of adaptation are. Methods: Quantitative 18F-FDG PET combined with the acquisition of real-time arterial inp ...

2013

Predicting Concentrations of Organic Chemicals in Fish by Using Toxicokinetic Models

Kristin Schirmer, Julita Maria Stadnicka-Michalak

Quantification of chemical toxicity continues to be generally based on measured external concentrations. Yet, internal chemical concentrations have been suggested to be a more suitable parameter. To better understand the relationship between the external a ...

2012

A two-compartment mathematical model of neuroglial metabolism using [1-C-11] acetate

Rolf Gruetter, Bernard Lanz

The purpose of this study was to develop a two-compartment metabolic model of brain metabolism to assess oxidative metabolism from [1-C-11] acetate radiotracer experiments, using an approach previously applied in C-13 magnetic resonance spectroscopy (MRS), ...

Nature Publishing Group2012

Mathematical Modeling of Brain Energy Metabolism, Measured with PET and MRS in Rodents

Bernard Lanz

Positron emission tomography (PET) and nuclear magnetic resonance spectroscopy (MRS) are two biomedical measurement techniques developed in the end of the XXth century, which drastically improved the amount of accessible information available in vivo. PET ...

EPFL2012

Toxicokinetic-toxicodynamic modelling of survival of Gammarus pulex in multiple pulse exposures to propiconazole: model assumptions, calibration data requirements and predictive power

Kristin Schirmer

Toxicokinetic-toxicodynamic (TKTD) models quantify the time-course of internal concentration, which is defined by uptake, elimination and biotransformation (TK), and the processes which lead to the toxic effects (TD). TKTD models show potential in predicti ...

Springer2012

Example-based Support Vector Machine for Drug Concentration Analysis

Giovanni De Micheli, Wenqi You Dubout

Machine learning has been largely applied to ana- lyze data in various domains, but it is still new to personalized medicine, especially dose individualization. In this paper, we focus on the prediction of drug concentrations using Support Vector Machines ...

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