A5011048809- Gene Regulatory Network Analysis
- Pharmacogenetics and Drug Metabolism
- Computational Drug Discovery Methods
- Receptor Mechanisms and Signaling
- Pharmaceutical studies and practices
- Hormonal Regulation and Hypertension
- Antibiotics Pharmacokinetics and Efficacy
- Drug Transport and Resistance Mechanisms
- Cell death mechanisms and regulation
- Blood Pressure and Hypertension Studies
- Pregnancy and Medication Impact
- Diabetes Treatment and Management
- Mathematical Biology Tumor Growth
- Pancreatic function and diabetes
- Electrolyte and hormonal disorders
- Protein Structure and Dynamics
- Drug Solubulity and Delivery Systems
- Retinal Diseases and Treatments
- 3D Surveying and Cultural Heritage
- Bioinformatics and Genomic Networks
- Retinopathy of Prematurity Studies
- Heart Failure Treatment and Management
- Ancient and Medieval Archaeology Studies
- Archaeological Research and Protection
- Pharmacological Effects and Toxicity Studies
Bayer (Germany)
2014-2024
University of Bamberg
2012-2024
Bayer (United States)
2015
University of Stuttgart
2004-2009
National University of Ireland, Maynooth
2006
The aim of this tutorial is to introduce the fundamental concepts physiologically based pharmacokinetic/pharmacodynamic (PBPK/PD) modeling with a special focus on their practical implementation in typical PBPK model building workflow. To illustrate basic steps building, for ciprofloxacin will be constructed and coupled pharmacodynamic simulate antibacterial activity treatment.
Apoptosis is an important physiological process crucially involved in development and homeostasis of multicellular organisms. Although the major signaling pathways have been unraveled, a detailed mechanistic understanding complex underlying network remains elusive. We translated here current knowledge molecular mechanisms death-receptor-activated caspase cascade into mathematical model. A reduction down to apoptotic core machinery enables application analytical methods evaluate system...
Today, in silico studies and trial simulations already complement experimental approaches pharmaceutical R&D have become indispensable tools for decision making communication with regulatory agencies. While biology is multiscale by nature, project work, software usually focus on isolated aspects of drug action, such as pharmacokinetics at the organism scale or pharmacodynamic interaction molecular level. We present a modeling simulation platform consisting PK-Sim(®) MoBi(®) capable building...
According to current US Food and Drug Administration ( FDA ) European Medicines Agency EMA guidance documents, physiologically based pharmacokinetic PBPK modeling is a powerful tool explore quantitatively predict drug‐drug interactions DDI s) may offer an alternative dedicated clinical trials. This study provides whole‐body models of rifampicin, itraconazole, clarithromycin, midazolam, alfentanil, digoxin within the Open Systems Pharmacology OSP Suite. All were built independently, coupled...
Because of the vulnerability and frailty elderly adults, clinical drug development has traditionally been biased towards young middle-aged adults. Recent efforts have begun to incorporate data from paediatric investigations. Nevertheless, often remain underrepresented in trials, even though persons aged 65 years older receive majority prescriptions. Consequently, a knowledge gap exists with regard pharmacokinetic (PK) pharmacodynamic (PD) responses subjects, leaving safety efficacy medicines...
Proteins are an increasingly important class of drugs used as therapeutic well diagnostic agents. A generic physiologically based pharmacokinetic (PBPK) model was developed in order to represent at whole body level the fundamental mechanisms driving distribution and clearance large molecules like proteins. The built extension PK-Sim for small incorporating (i) two-pore formalism drug extravasation from blood plasma interstitial space, (ii) lymph flow, (iii) endosomal (iv) protection by...
Many biological systems have the capacity to operate in two distinct modes, a stable manner. Typically, system can switch from one mode other response specific external input. Mathematically, these bistable are usually described by models that exhibit (at least) steady states. On hand, capture variability, it seems more natural associate each of operation an appropriate invariant set state space rather than single fixed point. A general formulation is proposed this paper, which allows...
Dose selection for "first in children" trials often relies on scaling of the pharmacokinetics from adults to children. Commonly used approaches are physiologically-based pharmacokinetic modeling (PBPK) and allometric (AS) combination with maturation clearance early life. In this investigation, a comparison two was performed provide insight into physiological meaning AS functions their interchangeability. The analysis focused established using paracetamol morphine paediatric data after...
This tutorial presents the workflow of adapting an adult physiologically based pharmacokinetic (PBPK) model to pregnant populations using Open Systems Pharmacology (OSP) software suite (www.open-systems-pharmacology.org). is illustrated a previously published PBPK for metronidazole that extrapolated pregnancy by parameterizing and extending structure in terms pregnancy-induced physiological changes. Importantly, this can be applied other scenarios where models need re-parameterized or...
Analyses of different robustness aspects for models the direct signal transduction pathway receptor-induced apoptosis is presented. Apoptosis a form programmed cell death, removing unwanted cells within multicellular organisms to maintain proper balance between reproduction and death. Its signalling includes an activation feedback loop that generates bistable behaviour, where two steady states can be seen as 'life' 'death'. Inherent robustness, widely recognised in biological systems, major...
On May 19, 2016, the US Food and Drug Administration (FDA) hosted a public workshop, entitled "Mechanistic Oral Absorption Modeling Simulation for Formulation Development Bioequivalence Evaluation."1 The topic of mechanistic oral absorption modeling, which is one major applications physiologically based pharmacokinetic (PBPK) modeling simulation, focuses on predicting by mechanistically integrating gastrointestinal transit, dissolution, permeation processes, incorporating systems, active...
Drug–drug interactions (DDIs) and drug–gene (DGIs) pose a serious health risk that can be avoided by dose adaptation. These are investigated in strictly controlled setups, quantifying the effect of one perpetrator drug or polymorphism at time, but real life patients frequently take more than two medications very heterogenous regarding their genetic background. The first objective this study was to provide whole-body physiologically based pharmacokinetic (PBPK) models important cytochrome...
Physiologically based pharmacokinetic (PBPK) models are increasingly used to support pediatric dose selection for small molecule drugs. In contrast, only a few PBPK therapeutic antibodies have been published recently, and the knowledge on maturation of processes relevant antibody pharmacokinetics (PK) is limited compared molecules. The aim this study was, thus, evaluate predictions from children which were scaled adults in order identify respective gaps. For this, we generic model...
This study provides whole-body physiologically-based pharmacokinetic models of the strong index cytochrome P450 (CYP)1A2 inhibitor and moderate CYP3A4 fluvoxamine sensitive CYP1A2 substrate theophylline. Both were built thoroughly evaluated for their application in drug-drug interaction (DDI) prediction a network perpetrator victim drugs, combining them with previously developed caffeine (sensitive substrate), rifampicin (moderate inducer), midazolam substrate). Simulation all reported...
Finerenone is a nonsteroidal selective mineralocorticoid receptor antagonist (MRA) that demonstrated efficacy in delaying the progression of chronic kidney disease (CKD) and reducing cardiovascular events patients with CKD type 2 diabetes mellitus FIDELIO-DKD, where 5734 were randomized 1:1 to receive either finerenone or placebo, median follow-up 2.6 years. Doses 10 20 mg once daily titrated based on (serum) potassium estimated glomerular filtration rate. The MRA mode action increases...
There are no data on pharmacokinetics, pharmacodynamics, and immunogenicity of intravitreal aflibercept in preterm infants with retinopathy prematurity (ROP). FIREFLEYE compared 0.4 mg/eye laser photocoagulation acute-phase ROP requiring treatment.