|Who should attend?
The course is suitable for Drug Discovery & Development Scientists e.g. pharmacologists, medicinal chemists, safety and clinical scientists, statisticians, pharmacokineticists, etc. The course is also of value to regulatory experts.
✚To raise awareness amongst bioscientist, medicinal chemists and clinical scientists of what kinetic dynamic (PKPD) methods can offer
✚To raise awareness of the individual steps that make up the dose-plasma-distribution-binding-turnover response process
✚To raise awareness of experimental design. Which investments have to be made early and late in discovery?
✚To raise the awareness of the level of agreement between in vitro and in vivo for drug potency
✚To build a case for the assessment of the first time in man dose
✚To provide theory and methods of in vivo PK & PD data using MAXSIM2 as a simulation tool
”MAXSIM2 is an easy to use, intuitive, and interactive application for physiologically based pharmacokinetic and pharmacodynamic (PBPKPD) simulation, developed at the Fraunhofer-Chalmers Research Centre for Industrial Mathematics (FCC) in close collaboration with Dr. Johan Gabrielsson. The simulation models in MAXSIM2 are physiologically based, which means that the pharmacokinetic and pharmacological processes are defined in terms of physiologically, anatomically, and biochemically interpretable parameters and mechanisms. In these models each organ is represented by one or
several compartments, which are interconnected by blood flow. These types of models are excellent tools for real-time presentation of the interplay between physiology, pharmacology, and pharmacokinetic processes. MAXSIM2 also includes a variety of pharmacodynamic models, such as instantaneous concentration-response models, distributional models, and turnover models. MAXSIM2 is an ideal application for both educational and commercial use where thorough understanding of pharmacodynamic
and pharmacokinetic phenomena is important”. Delegates must bring their own laptops to the course.
Delegates must bring their own laptops to the course.
|September 10, 2014|
||1. Introduction and mental contract|
• What are our expectations
• Course layout & course material
|| 2. Review of basic PK concepts|
• Review of Cl, Vss & t1/2 from a PD point of view
• Steady-state, exposure
• IV vs. extravascular dosing
• Review of basic PPB concepts Cu, C & fu
• When does plasma protein binding matter?
||3. Pharmacodynamics A (Equilibrium) |
• Review of Steady-state models
• Efficacy, potency, specificity and selectivity
• Kinetics of drug action
• Design issues and Case Studies
||4. Maxsim2 exercise|
• Simulate single and multiple dose PK
• Simulate single and multiple dose PD
||5. Inter-species scaling|
• Review scaling & allometry from a PD point of view
• Why animals differ wrt turnover of drugs
• Why do we build a dose nomogram?
||6. Groups exercise(s) I|
• Prediction of the human dose and PK/PD profile from preclinical data
|Wrap-up of the day and the group exercise |
|September 11, 2014|
||7. Pharmacodynamics B (Time delays)|
• Steady-state models vs. time delay
• Basic concepts on distributional delays
• Turnover concepts and how to model
8. Case Studies
• Project example(s)
• Dose nomogram
• Summarizing the effective concentration range
||9. Introduction to Groups exercise II|
• Compound selection from PK/PD data, assessment of safety margins and selection human dose.
||Summary of Group exercise & Wrap-up of course|
||✚Pharmacokinetics from a pharmacological point of view.
✚PK half-life vs. half-life of response.
✚The apparent disconnection between concentration and response.
✚Effect compartment models (distribution-rate limited)
✚Turnover models (indirect response)
✚Receptor on/off binding models
✚Scaling PK and PD properties to man
✚Practical experimental design of PD studies
✚Integration of PK/PD reasoning and simulations in drug projects
✚PK&PD assessment at milestone decisions
Johan Gabrielsson has been Senior Principal Scientist at AstraZeneca R&D Mölndal. His responsibilities included kinetic/dynamic related project tasks in the CV & GI & CNS & Cancer & Biologics areas. He is author of the textbook ‘Pharmacokinetic and Pharmacodynamic Data Analysis: Concepts and Applications’ 4th ed. (2006). He is professor of Integrative Pharmacology at the Swedish Agricultural University in Uppsala, Sweden. He is also academically affiliated with Dept. of Pharmaceutics, Univ. Tennessee and University of Manchester. He has published extensively in the field of pharmacokinetic-pharmacodynamic modelling and reasoning, and has run numerous courses internally and externally in the area of biological data analysis since 1985 in Europe, the US and Asia (>5000 participants) at both the undergraduate and graduate level. His research focuses on modelling different aspects of endogenous turnover, such as functional tolerance and rebound phenomena, physiological limits and target-mediated drug disposition in collaboration with Professor LA Peletier, Leiden University. He has been external examiner on several PhD Theses outside of Sweden.
Rasmus Jansson-Löfmark is a Senior Modelling and Simulation scientist at AstraZeneca R&D Mölndal. Rasmus responsibilities include preclinical PK/PD related tasks, such as study designs, analysis; and provides strategic input and interpretation of data in cardiovascular and metabolic diseases. He received his PhD thesis in 2009 and has since then been working at AZ with focus on PK/PD application in drug projects ranging from project startup to CD nomination. He has also been a teacher in PK/PD at Gothenburg University and been involved in several PK/PD courses within the company. He is/has been a co-supervisor for PhD Students within the academia and industry.
"Quantitative Pharmacology, An Introduction to Integrative Pharmacokinetic-Pharmacodynamic Analysis" willl be used during the course and is included in the fee.
It will be handed out at registration.
This textbook introduces the basics of PK and PD concepts• outlines the implications of integrating PK and PD analysis• introduces the principles behind different biomarkers and inter-species scaling• discusses experimental design of PK, PD and safety studies in non-human species• covers numerous real life Case Studies from the drug discovery arena.
|Time and Location
This course will take place on September 10-11, 2014 at the Maritim Hotel München which is located only a 10-minute walk from the central train station, it's also close to the city’s most famous historical landmarks. In addition to these renowned sightseeing attractions, the hotel’s immediate neighborhood is dominated by an inspiring multicultural atmosphere. Turkish shops offer fresh fruit and vegetables for bargain prices and all sorts of exotic gifts for travelers.
|Application, Confirmation, Cancellation etc
The participation fee is EUR 1400 (All prices are VAT exclusive and VAT 25% will be added). The fee includes course documentation, the textbook "Quantitative Pharmacology, An Introduction to Integrative Pharmacokinetic-Pharmacodynamic Analysis", coffee-breakes, lunches and a course dinner.
A number of hotel rooms have been booked at the Maritim Hotel München at preferential rates between Tuesday, September 9 – Thursday, September 11, 201. The price for a single room is EUR 235/night (VAT exclusive) including breakfast.
Delegates will be registered upon receipt of the completed form and a first confirmation will be sent by e-mail.
The number of seats are limited and early booking is strongly recommended.
Detailed course information will be sent out approximately two weeks before the event. An invoice will be sent separately and the payment must be settled before the start of the course.
Cancellations should be addressed, in writing, to the Swedish Academy of Pharmaceutical Sciences.
• Cancellation can be made free of charge until July 27, 2014
• No refunds will be made after July 27, 2014
Substitutions may however be made at any time. Kindly forward the name of the substitute to the Swedish Academy of Pharmaceutical Sciences.