HOME- R&D
- Bryn Mawr Conference
- Hyderabad Conference
- Workshops & Training
- 2009 Oxford (Discovery)
- 2009 Oxford (ADMET)
- 2009 Hyderabad
- 2008 Oxford
- 2007 Oxford
- Biggin, P
- Bolger, M
- DiBella, J
- Dudgeon, T
- Gata-Aura, J
- Goodman, J
- Hardy, B
- Hawkins, P
- Kontoyianni, M
- Maginn, S
- Plonka, W
- Reid, D
- Uhrig, U
- 2006 Oxford
- Program
- Exhibition
- Registration
- Jobs
- Contact
- Schedule
|
|
|
|
|
|
|
John DiBella is a Senior Scientist and Business Development Manager at Simulations Plus, Inc. in Lancaster, California, USA. He obtained B.S. and M.S. degrees (with honors) in Biomedical Engineering from Case Western Reserve University in 2003. His graduate research was focused on computational modeling of physiological systems.
John joined Simulations Plus in 2003 and has spent time working on the development of GastroPlus (oral absorption and pharmacokinetic simulation tool) and DDDPlus (simulation of the in vitro dissolution experiment) while also involved in business development activities.
|
|
| Workshop, 14 September 2007, Chemistry Research Laboratory, Oxford University |
|
In silico Modeling of Gastrointestinal Simulation and Physiologically-based Pharmacokinetics
Workshop Instructor: John Di Bella, Simulations Plus
Using GastroPlus this workshop will provide an overview of gastrointestinal physiology and compartmental absorption and transit simulation models. The class will work on hands-on integration of biopharmaceutical properties and formulation factors by using gastrointestinal simulation, physiologically-based pharmacokinetics, parameter sensitivity analysis and virtual clinical trials.
The following topics will be covered:
I. Organization of Input Data
A. File types (getting data out of ISISBase and into .sdf format)
B. ADMET Predictor Export to GastroPlus (Drug Table and Acid Base Table)
II. GastroPlus ACAT model
A. Physiological models
B. Physicochemical properties
C. Solubility model
D. Formulation considerations
E. Absorption
F. Pharmacokinetics model
G. Metabolism and Transporter Module
III. Drug database structure and tables
IV. Support files
A. Plasma concentration-time – oral and IV (.opd and .ipd)
B. Solubility vs pH (.spd)
C. Luminal degradation rate vs pH (.cdd)
D. Controlled release and in vitro dissolution-time (.crd and .dsd)
E. Pharmacodynamic effect vs time (.efd)
F. ACAT model (.cat)
V. Outputs and Graphics
A. Parameter Sensitivity Analysis
B. Virtual Trial Stochastic Simulations
C. Optimization output
VI. PBPK Background and Principles
A. Why and when PBPK vs. compartmental PK?
B. Perfusion-limited vs. Permeability-limited models
C. In silico generation of organ physiology (PEAR)
D. In silico calculation of tissue:plasma partition coefficients.
VII. PKPlus™ Module – fitting IV pharmacokinetics
VIII. PDPlus™ Module – pharmacodynamics module
|
In silico Modeling of Absorption, Distribution, Metabolism, Excretion, and Toxicity Properties
Workshop Instructor: John Di Bella, Simulations Plus
In silico models of biopharmaceutical, pharmacokinetic, and physiological properties related to absorption, distribution, metabolism, excretion, and toxicity (ADMET) have become a valuable tool for reducing the number of experiments that need to be conducted in order to find drug candidates with less chance of failure during development. Application of the estimated properties and/or measured in vitro properties in a physiologically-based gastrointestinal simulation to predict fraction absorbed, bioavailability, and Cp vs. Time profiles in discovery, development, pre-clinical, and clinical phases of pharmaceutical development can be considered to be a means of integrating the various calculated and measured properties to enhance decision making.
This workshop is intended to provide the attendees with lecture and hands-on experience in using in silico tools for drug discovery and development. The workshop will present general information about publicly available sources of data for model building, concepts and schematic outlines of model building methods, and knowledgeable interpretation and analysis of results. The hands-on part of the course will provide exposure to several software tools from Simulations Plus, Inc. that can be used for ADMET property estimation and gastrointestinal simulation.
Using ADMET Predictor the class will be introduced and work with examples on properties and models of interest in early ADMET, log P, log D, pKa, native solubility, solubility in buffer, solubility in bio-relevant media, pH dependence of solubility, effective permeability, apparent permeability, diffusivity, dissolution rate, fraction absorbed, bioavailability, volume of distribution, clearance, plasma protein binding, carcinogenicity, mutagenicity, maximal recommended therapeutic dose, and hERG K+ channel inhibition. Hands-on calculations will be made of properties for single molecules and databases of drugs with known fraction absorbed or human effective permeability.
All attendees will receive ADMET Predictor and GastroPlus installation CDs. These programs run under MS-Windows and a fully functional version may be unlocked for an evaluation period by contacting Simulations Plus.
|
| Workshop, 14 September 2007, Chemistry Research Laboratory, Oxford University |
|
|
|
|
|
|
|
|
|
