Non-linear Time Scaling for IVIVC: Secrets from an Expert

Speaker(s): Jean-Michel Cardot
Date: March 29, 2017
Time: 11 am EST
Duration: 1 hour

In vitro-in vivo correlation (IVIVC) is a predictive mathematical tool that describes the relationship between an in vitro property of a drug dosage form and an in vivo pharmacokinetic response. IVIVCs generally employ linear time scaling. Yet sometimes, the IVIVC relationship is better described by a more complex function. For example, some drugs release in vivo at 2 different rates. The release rates for erodible matrices depends on the dosage form’s position in the intestine. For implants, the release rate changes as diffusion is followed by erosion.

If the in vitro test does not account for these possibilities, the in vitro dissolution may exhibit a different shape compared to in vivo release. In this case, a non-linear relationship must be established. Prof. JM Cardot will explain how non-parametric approaches can be used to determine time scaling.

About Our Speaker

Webinar-1speaker-CardotJean-Michel Cardot is a professor and head of the Department of Biopharmaceutics and Pharmaceutical Technology at the Auvergne University in France. Prior to coming to Auvergne University, he worked in the pharmaceutical industry for 15 years. Prof. Cardot earned degrees in pharmacy (PharmD), a Masters in Biopharmaceutical, Statistical sciences and Pharmacokinetics, and a doctorate in pharmaceutical sciences from Auvergne University. His research interests include biopharmaceutical development of drugs, in vitro dissolution, and in vivo bioequivalence and in vitro-in vivo correlation.

Speaking into the Ether: Challenges of the Virtual Pharma Workplace

Speaker(s): Peter Bonate, Stacey Tannenbaum
Date: April 19, 2017
Time: 11 am EDT
Duration: 1 hour

In today’s global pharma workplace, virtual interactions are sometimes more common than live exchanges. We frequently use technology like WebEx or telephone to communicate with others. This presents problems and challenges not seen with face-to-face interactions, where there is visible feedback between the senders and receivers.

Since you can’t see (and sometimes can’t hear) your audience, you can’t read their facial expressions or body language during your presentation, and you can’t see them taking out their phones to play Candy Crush! How do you make your presentation engaging to combat multitasking?  How do you gauge if the audience understands what you’re saying?  How do you know they are not bored? How do you know they found your joke funny?

What kind of technology tools can facilitate connection with your audience?  What do you do when the technology fails?

What are some cultural issues that make presentations to a global group challenging? How should you change your style, language, or content to meet the needs of diverse audiences? In particular, how can modelers more effectively communicate results to non-modelers?

How do you efficiently deal with Q&A and feedback? Is it better to stop periodically to ask for questions or take them all at the end? What if there are NO questions- what does that mean?

In this webinar (a virtual presentation!), Drs. Peter Bonate and Stacey Tannenbaum will discuss these topics and other difficulties of speaking into the ether, and offer practical solutions that you can use to strengthen your collaboration in the virtual workplace.

About Our Speakers

Peter Bonate has more than 20 years industrial experience and is the Executive Director of Pharmacokinetics, Modeling, and Simulation at Astellas. He is a fellow of the American Association of Pharmaceutical Scientists and American College of Clinical Pharmacology. In 2015 he was the recipient of the AAPS Research Achievement Award in Clinical Pharmacology. A recognized expert in modeling and simulation, his books are used in classrooms around world and he is a frequent speaker at webinars and conferences. His most recent book, Be a Model Communicator, discusses the problems and challenges of presentation modeling and simulation results to a non-technical audience.

Stacey Tannenbaum has almost 15 years of industrial experience and is a Director of Pharmacokinetics, Modeling, and Simulation at Astellas Pharma.  She has had significant impact on the global Pharmacometrics community by co-founding the International Society of Pharmacometrics (ISoP)  and the local NJ-based networking group Modeling and Simulation Applications in Clinical Pharmacotherapy (MoSAiC). Stacey also co-founded the American Conference on Pharmacometrics (ACoP), and is the Chair of the Executive Committee for the 2020 World Conference on Pharmacometrics (WCoP). She serves as a Member-at-Large for the AAPS Executive Council.

Mechanistic Modeling of Genome Scale Molecular Interaction Networks

Speaker(s): Andrzej Kierzek
Date: April 26, 2017
Time: 11am EDT
Duration: 1 hour

Physiologically-based Pharmacokinetic (PBPK) modeling has become the industry standard for predicting drug-drug interactions, formulation effects, and pharmacokinetics in human populations. As a bottom-up, literature-based, mechanistic computer simulation approach, it shares general methodology with the computational systems biology, where molecular biology knowledge is assimilated into molecular network models. In particular, reconstruction of Genome Scale Metabolic Networks (GSMNs) has led to mechanistic models incorporating a whole set of metabolic enzymes expressed in human tissues. Moreover, dynamic models of the expression of key drug metabolism enzymes are available.

Currently, PBPK models account for about 20 genes involved in drug metabolism. Integrating PBPK with GSMN and gene regulation models can extend the scope of mechanistic pharmacokinetic modeling to thousands of genes as well as the complex interactions of drug metabolism enzymes with endogenous metabolites such as cortisol. In this webinar, Dr. Andrzej Kierzek will demonstrate how integrating human hepatocyte GSMN, gene regulation of CYP3A4, and a basic PBPK model can identify genes influencing the production of toxic metabolites and simulate kinetics of this metabolite as a function of cortisol and Pregnane X receptor (PXR) ligands.

About Our Speaker

Andrzej Kierzek graduated with an undergraduate degree in molecular biology from the University of Warsaw and received a PhD in biophysics from Polish Academy of Sciences in 1999. Since 2004, he has been working at University of Surrey, UK and became Professor of Systems Biology in 2011. In April 2016, he moved to Certara QSP as Head of Systems Modeling. He is still a visiting Professor of Systems Biology at Surrey. Andrzej has more than 20 years of experience in computational biology. He has been working in computational systems biology for over 15 years. He published models and software for analysis of molecular network dynamics and constraint-based modeling of genome scale metabolic networks, including metabolic reprogramming in cancer. Currently, his research focus is on immune-oncology and immunogenicity.

Modeling PK/PD Systems with Distributed Delays

Speaker(s): Wojciech Krzyzanski
Date: May 16, 2017
Time: 11 am EST
Duration: 1 hour

Systems with distributed delays are extensions of systems with discrete delays where a single lag time is represented by a distribution of lag times. Distributed absorption times for orally administered drugs serve as an example of a pharmacokinetic (PK) system with distributed delays. Another example is a hematopoietic cell population with distributed lifespans.

The topic of this webinar is to introduce mathematical tools to model pharmacokinetic/pharmacodynamic (PK/PD) systems with distributed delays. These models will be implemented in Phoenix NLME by means of the delay() operator. A distributed delay version of the transit compartment model for oral drug absorption will be provided. A distributed lifespan PD model of RBC production will be also discussed.

About Our Speaker

Dr. Wojciech Krzyzanski is an Associate Professor of Pharmaceutical Sciences at the University at Buffalo, State University of New York (UB). Dr. Krzyzanski holds a PhD in applied mathematics and a MA in pharmacology. His PK/PD modeling interests and capabilities include the modeling of pharmacokinetics and pharmacodynamics of hematopoietic growth factors, the model-based development of optimal dosing regimens for chemotherapy induced cytotoxicities, particularly myelosuppression, the pharmacometric analysis of properties of various types of indirect response models, and the evolution of target-mediated PK/PD models.

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