Refine
Year of publication
- 2016 (284) (remove)
Institute
- Fachbereich Medizintechnik und Technomathematik (54)
- Fachbereich Chemie und Biotechnologie (44)
- Fachbereich Bauingenieurwesen (35)
- Fachbereich Elektrotechnik und Informationstechnik (35)
- IfB - Institut für Bioengineering (35)
- Fachbereich Wirtschaftswissenschaften (31)
- Fachbereich Luft- und Raumfahrttechnik (28)
- Fachbereich Maschinenbau und Mechatronik (26)
- Fachbereich Energietechnik (17)
- INB - Institut für Nano- und Biotechnologien (15)
Document Type
- Article (118)
- Conference Proceeding (81)
- Part of a Book (29)
- Book (25)
- Other (10)
- Conference: Meeting Abstract (8)
- Report (6)
- Doctoral Thesis (3)
- Part of a Periodical (2)
- Patent (1)
Keywords
- Technical Operations Research (2)
- Additive Manufacturing (1)
- Annulus Fibrosus (1)
- Archeology (1)
- Assessment (1)
- Asymptotic efficiency (1)
- Bacillus atrophaeus (1)
- Balance (1)
- Balanced hypergraph (1)
- Brandfall (1)
- Building Culture (1)
- Building Systems (1)
- Business Simulations (1)
- Cardiac myocytes (1)
- Cardiac tissue (1)
- Cartography (1)
- CellDrum (1)
- Censored data (1)
- Co-managed care (1)
- Collaborative robot (1)
- Computational biomechanics (1)
- Controller Parameter (1)
- DNA biosensor (1)
- Designpraxis (1)
- Disc Degeneration (1)
- Diversity (1)
- Drinking Water Supply (1)
- Drug simulation (1)
- Duality (1)
- EN 1993-1-2 (1)
- Effizienz (1)
- Einbetten in das Internet der Dinge (1)
- Elderly (1)
- Electromechanical modeling (1)
- Engineering Education (1)
- Eutectic Silver Copper alloy (1)
- External knee adduction moments (1)
- Fall prevention (1)
- Field effect (1)
- Forschung, pränormativ (1)
- Frequency adaption (1)
- Gamification (1)
- Gender (1)
- Ground-level falls (1)
- Hall’s Theorem (1)
- Heart tissue culture (1)
- Higher Education (1)
- Hodgkin–Huxley models (1)
- Homogenization (1)
- Human-Robot interaction (1)
- Hypergraph (1)
- Hypothesentests (1)
- Induced pluripotent stem cells (1)
- Infrastructures (1)
- Inotropic compounds (1)
- Intervertebral Disc (1)
- Intradiscal Pressure (1)
- Inverse dynamic problem (1)
- Inverse kinematic problem (1)
- Ion channels (1)
- Koenig’s Theorem (1)
- LAPS (1)
- Label-free detection (1)
- Land Survey and Measurement Systems (1)
- Layer-by-layer adsorption (1)
- Level Control System (1)
- Manipulated variables (1)
- Matching (1)
- Minimal-Ansatz für Embedded-Systeme (1)
- Mixed Integer Programming (1)
- Mixed-Integer Nonlinear Optimisation (1)
- Mobility (1)
- Mobility tests (1)
- Musculoskeletal model (1)
- Nucleus Pulposus (1)
- Optimal Closed Loop (1)
- Optimal Topology (1)
- Optimization (1)
- Parametric Design (1)
- Parametric Modelling (1)
- Path planning (1)
- Pharmacology (1)
- Poly(allylamine hydrochloride) (1)
- Porositat (1)
- Product-integration (1)
- Reference Process Model (1)
- Referenzmodellierung (1)
- Response Surface Method (1)
- SLM (1)
- Safety concept (1)
- Semi-parametric random censorship model (1)
- Serious Games (1)
- Solver Per- formance (1)
- Structuralist Architecture (1)
- Subject-oriented Business Process Management (1)
- Survival analysis (1)
- System Design (1)
- System Design Problem (1)
- TM Forum (1)
- TTIP (1)
- Technical Operation Research (1)
- Telecommunications Industry. (1)
- Tinetti test (1)
- Tragwerksbemessung (1)
- Unternehmensarchitektur (1)
- Unternehmenstransformation (1)
- Vergleich von Experimenten (1)
- Vertex cover (1)
- Volterra integral equation (1)
- Workspace monitoring (1)
- biosensors (1)
- building industry (1)
- chemical sensor (1)
- diversity (1)
- eTOM (1)
- efficiency (1)
- electronic communications markets (1)
- endospores (1)
- energy disspation (1)
- engineering education (1)
- enhanced Telecom Operations Map (eTOM) (1)
- friction (1)
- hiPS cardiomyocytes (1)
- immobilization (1)
- impulsive effects (1)
- industrial research (1)
- ingot (1)
- innovation (1)
- iron and steel industry (1)
- liberalisation (1)
- light-addressable potentiometric sensor (1)
- liquid-storage tank (1)
- liquid-structure interaction (1)
- materials technology (1)
- metal structure (1)
- organosilanes (1)
- plug-based microfluidic device (1)
- regulation (1)
- research project (1)
- research report (1)
- resistance of materials (1)
- seismic response (1)
- silanization (1)
- social responsible engineering (1)
- steel (1)
- structural design (1)
- structure-soil-structure interaction (1)
- testing hypotheses (1)
- wave run-up (1)
NVS123 is a poorly water-soluble protease 56 inhibitor in clinical development. Data from in vitro hepatocyte studies suggested that NVS123 is mainly metabolized by CYP3A4. As a consequence of limited solubility, NVS123 therapeutic plasma exposures could not be achieved even with high doses and optimized formulations. One approach to overcome NVS123 developability issues was to increase plasma exposure by coadministrating it with an inhibitor of CYP3A4 such as ritonavir. A clinical boost effect was predicted by using physiologically based pharmacokinetic (PBPK) modeling. However, initial boost predictions lacked sufficient confidence because a key parameter, fraction of drug metabolized by CYP3A4 (ƒₘCYP3A4), could not be estimated with accuracy on account of disconnects between in vitro and in vivo preclinical data. To accurately estimate ƒₘCYP3A4 in human, an in vivo boost effect study was conducted using CYP3A4-humanized mouse model which showed a 33- to 56-fold exposure boost effect. Using a top-down approach, human ƒₘCYP3A4 for NVS123 was estimated to be very high and included in the human PBPK modeling to support subsequent clinical study design. The combined use of the in vivo boost study in CYP3A4-humanized mouse model mice along with PBPK modeling accurately predicted the clinical outcome and identified a significant NVS123 exposure boost (∼42-fold increase) with ritonavir.