A5022371964- Pharmacogenetics and Drug Metabolism
- nanoparticles nucleation surface interactions
- Pharmaceutical studies and practices
- Statistical Methods in Clinical Trials
- Atrial Fibrillation Management and Outcomes
- Blood Coagulation and Thrombosis Mechanisms
- Health Systems, Economic Evaluations, Quality of Life
- Computational Drug Discovery Methods
- Venous Thromboembolism Diagnosis and Management
- Advanced Causal Inference Techniques
- Pharmaceutical Economics and Policy
- Cardiac Arrhythmias and Treatments
- Cardiac electrophysiology and arrhythmias
- Blood Pressure and Hypertension Studies
- Fluid Dynamics and Thin Films
- Innovative Microfluidic and Catalytic Techniques Innovation
- Biochemical and Molecular Research
- Artificial Intelligence in Healthcare
- Stochastic processes and statistical mechanics
- Cardiovascular Function and Risk Factors
- Machine Learning in Healthcare
- Adhesion, Friction, and Surface Interactions
- Material Dynamics and Properties
- Chronic Disease Management Strategies
- Diabetes Management and Research
Bayer (Germany)
2014-2025
University of Florida
2019
Columbus Oncology and Hematology Associates
2019
Bayer (United States)
2014
Heinrich Heine University Düsseldorf
1996-2000
This document was developed to enable greater consistency in the practice, application, and documentation of Model-Informed Drug Discovery Development (MID3) across pharmaceutical industry. A collection "good practice" recommendations are assembled here order minimize heterogeneity both quality content MID3 implementation documentation. The three major objectives this white paper to: i) inform company decision makers how strategic integration can benefit R&D efficiency; ii) provide analysts...
Venous thromboembolism has been increasingly recognised as a clinical problem in the paediatric population. Guideline recommendations for antithrombotic therapy patients are based mainly on extrapolation from adult trial data, owing to limited number of trials populations. The oral, direct Factor Xa inhibitor rivaroxaban approved several thromboembolic disorders, and its well-defined pharmacokinetic pharmacodynamic characteristics efficacy safety profiles adults warrant further investigation...
The EINSTEIN-Jr program will evaluate rivaroxaban for the treatment of venous thromboembolism (VTE) in children, targeting exposures similar to 20 mg once-daily dose adults. A physiologically based pharmacokinetic (PBPK) model pediatric dosing has been constructed.We quantitatively assessed pharmacokinetics (PK) a single children using population (PopPK) modelling and applicability PBPK model. Plasma concentration-time data from phase I study were analysed by non-compartmental PopPK analyses...
Abstract As a leading cause of death and morbidity, heart failure (HF) is responsible for large portion healthcare disability costs worldwide. Current approaches to define specific HF subpopulations may fail account the diversity etiologies, comorbidities, factors driving disease progression, therefore have limited value clinical decision making development novel therapies. Here we present data-driven approach understand characterize real-world manifestation by clustering symptom-related...
In 2017, the free and open-source software Open Systems Pharmacology (OSP) was launched. Since then, OSP has evolved from a small community into diverse network of stakeholders committed to advancing solutions for model-informed drug development (MIDD). this context, first Community Conference hosted by Novartis in Basel, Switzerland, on October 7-8, 2024, which gathered over 100 attendees more than 40 institutions. This perspective synthesizes key insights conference.
Heart failure (HF) is a leading cause of morbidity, healthcare costs, and mortality. Guideline based segmentation HF into distinct subtypes coarse unlikely to reflect the heterogeneity etiologies disease trajectories patients. While analyses electronic health records show promise in expanding our understanding complex syndromes like an evidence-driven way, limitations data quality have presented challenges for large-scale EHR-based insight generation decision-making. We present...
Abstract Since the Open Source Initiative laid foundation for open source software environment in 1998, popularity of free and has been steadily increasing. Model‐informed drug discovery development (MID3), a key component pharmaceutical research development, heavily makes use computational models which can be developed using various including Systems Pharmacology (OSP) (PK‐Sim/MoBi), tool physiologically based pharmacokinetic (PBPK) modeling. In this study, we aimed to investigate impact,...
Rivaroxaban is an oral, direct Factor Xa inhibitor approved in the European Union and several other countries for prevention of venous thromboembolism adult patients undergoing elective hip or knee replacement surgery advanced clinical development treatment thromboembolic disorders. Its mechanism action antithrombin independent differs from that anticoagulants, such as warfarin (a vitamin K antagonist), enoxaparin (an indirect thrombin/Factor inhibitor) dabigatran thrombin inhibitor). A...
Development and guidance of dosing schemes in children have been supported by physiology-based pharmacokinetic (PBPK) modeling for many years. PBPK models are built on a generic basis, where compound- system-specific parameters separated can be exchanged, allowing the translation these from adults to accounting physiological differences. Owing features, is valuable approach support clinical decision making children. In this analysis, we evaluate pediatric 10 small-molecule compounds that...
Decompensation is a hallmark of disease progression in cirrhotic patients. Early detection phase transition from compensated cirrhosis to decompensation would enable targeted therapeutic interventions potentially extending life expectancy. This study aims (a) identify the predictors large, multicentric cohort patients with cirrhosis, (b) build reliable prognostic score for and (c) evaluate independent cohorts.Decompensation was identified electronic health records data 6049 IBM Explorys...
The long-lasting anticoagulant effect of vitamin K antagonists can be problematic in cases adverse drug reactions or when patients are switched to another therapy. objective this study was examine silico the rivaroxaban, an oral, direct Factor Xa inhibitor, combined with residual discontinued warfarin. Our simulations were based on recommended dosing regimen for stroke prevention atrial fibrillation. effects combination warfarin plus rivaroxaban simulated using extended version a previously...
Introduction The acute respiratory distress syndrome (ARDS) is a highly relevant entity in critical care with mortality rates of 40%. Despite extensive scientific efforts, outcome-relevant therapeutic measures are still insufficiently practised at the bedside. Thus, there clear need to adhere early diagnosis and sufficient therapy ARDS, assuring lower multiple organ failure. Methods analysis In this quality improvement strategy (QIS), decision support system as mobile application (ASIC app),...
Abstract Vericiguat (Verquvo; US: Merck, other countries: Bayer) is a novel drug for the treatment of chronic heart failure. Preclinical studies have demonstrated that primary route metabolism vericiguat glucuronidation, mainly catalyzed by uridine diphosphate‐glucuronosyltransferase (UGT)1A9 and to lesser extent UGT1A1. Whereas drug–drug interaction (DDI) study UGT1A9 inhibitor mefenamic acid showed 20% exposure increase, effect UGT1A1 inhibitors has not been assessed clinically. This...
A physiologically based kidney model was developed to analyze the renal excretion and exposure of hydrophilic agents, in particular contrast media, rats. In order study influence osmolality viscosity changes, mechanistically represents urine concentration by water reabsorption different segments tubules dependent tubular fluid flow. The established using experimental data on physiological steady state without administration any media or drugs. These included sodium urea gradient along...
Introduction The European Sleep Apnea Database was used to identify distinguishable obstructive sleep apnoea (OSA) phenotypes and investigate the clinical outcome during positive airway pressure (PAP) treatment. Method Prospective OSA patient data were recruited from 35 clinics in 21 countries. Unsupervised cluster analysis (anthropometrics, variables) performed a random sample (n=5000). Subsequently, all patients assigned clusters using conditional inference tree classifier. Responses PAP...
Copanlisib is an intravenously administered phosphatidylinositol 3-kinase (PI3K) inhibitor which was investigated in pediatric patients with relapsed/refractory solid tumors. A model-informed approach undertaken to support and confirm empirically selected starting dose of 28 mg/m2 for ≥1 year old, corresponding 80% the adult recommended adjusted body surface area. An physiologically based pharmacokinetic (PBPK) model initially established using copanlisib physicochemical disposition...