AT THE UNIVERSITY OF TORINO
Date 3/19/2002
Location: Villa Gualino - Viale Settimio Severo 65 - 10133 Torino Italy
Language: English
9.00 Opening Remarks: Trends and Perspectives of the population approach in Pharmacology and Clinical practice - Prof. M. Eandi
9.15 Population Modelling – Prof. D.Verotta
9.40 Non parametric Model analysis – Prof. R. Jelliffe
10.05 PKPD: Population analysis – Dr. R. Gomeni
10.30 Coffee Break
11.00 The application of Parzen method to population analysis – Dr. M. Costa
11.25 Markov Chain Monte Carlo – Prof. De Nicolao e Prof. Magni
11.50 Population PK in preclinical drug development - Dr. I. Poggesi
12.15 General Discussion
13.00 Lunch
14.00 Optimising drug in infective disease - Prof. Jelliffe
14.20 Individualising therapy in infective disease – Italian speaker to be confirmed
14.40 Optimizing drugs in neuropsychiatry - Prof. I. Bondareva
15.00 Genetic and environmental factors causing variability in psychotropic drugs pk - Prof. E. Spina
15.20 Coffee Break
16.00 Optimising transplant chemotherapy - Prof. N. O. Hoem
16.20 Optimising drugs in cancer chemotherapy - Dr. Bleyzac
16.40 Individualising cancer chemotherapy – Prof. R. Danesi
17.00 New approaches in dose optimization of 5-Fluorouracil – Dr. M. Gusella, Prof. R. Padrini
17.20 Optimising drugs in cardiology - Prof. R. Jelliffe
17.40 Individualising anticoagulant therapy – Dr. M.G. Scordo, Prof. R. Padrini, Prof. E. Spina
18.00 General Discussion and Closing remarks
International invited speakers:
Irina Bondareva, Ph.D.
Laboratory of Mathematical Medicine
Institute for Physical and Chemical Medicine
Moscow, Russia
Nathalie Bleyzac, Pharm.D.
Hospital Debrousse, Lyon, France
Nils Ove Hoem, Ph.D.
Associate Professor of Pharmacology,
Department of Pharmacology
School of Pharmacy
University of Oslo, Norway
Roger Jelliffe, M.D.
Professor of Medicine
Division of Geriatric Medicine
Director, Laboratory of Applied Pharmacokinetics
School of Medicine
University of Southern California, Los Angeles USA
Davide Verotta, Ph.D.
Associate Professor
Department of Biopharmaceutical Sciences
School of Pharmacy
University of California, S. Francisco USA
Prof. Mario Eandi MD mario.eandi@unito.it
Department of Anatomy and Pharmacology
Via P. Giuria 13
University of Torino - Italy
Organizing secretary
Roberto Passera, PharmD roberto.passera@tin.it
Gian Paolo Zara MD gianpaolo.zara@unito.it
Department of Anatomy and Pharmacology
Via P. Giuria 13
University of Torino - Italy
Phone: +39 011 6707803
Fax: +39 011 6707788
Admission to the Symposium: free
Registration to the Symposium: please send an e-mail or a Fax to the Organizing Secretary
Housing Information: Please contact
CO.AL.PI
Miss Silvia Pasquini
Phone +39 011
5613760
Fax +39 011 5621738
E-Mail: hotelres@hotelres.it
Workshop
A Hands-on workshop on parametric and nonparametric population PK and PD modelling and its application in therapeutic drug monitoring: WIN-USC*PACK
The USC Laboratory of Applied, and the School of Medicine, University of Torino, Department of Anatomy Pharmacology Italy, are pleased to announce a Three-Day, Hands-on workshop on
Principles of Pharmacokinetics - Parametric and Nonparametric Population PK and PD Modeling - Applications to Therapeutic Drug Monitoring and to Optimal Individualization of Drug Therapy
This course is intended for physicians, pharmacists and biomedical scientists with an interest in population pk/pd modeling, and also for those interested in therapeutic drug monitoring and optimally precise individualization of drug therapy for patient care.
Prior experience in clinical pharmacokinetics will be an advantage. Participants will be introduced to the USC*PACK software, which can be used both for therapeutic drug monitoring and optimal individualization of drug dosage regimens, as well as for parametric and nonparametric population PK/PD and physiological modeling.
This course will also introduce the new Win*USC*PACK software for "Multiple Model" design of dosage regimens that hit target goals with maximal precision. This method is based first on nonparametric population models. It also obtains a patient's Bayesian posterior nonparametric individual model, and, if needed, to detect and quantify the interoccasional variability in each patient's individual model, thus permitting detection of unsuspected changes in parameter values such as take place with the volume of distribution (and other parameters), in aminoglycoside antibiotics, for example, with changes in the patient's status. This sequential Bayesian "Interacting Multiple Model" Bayesian approach to interoccasional intra-individual variability comes from the aerospace community, where it is used to track evasive targets. It is new, to our knowledge, in the pharmacokinetic community. It is designed to track the behavior of drugs, especially in unstable patients, with maximum precision, to detect unsuspected changes in a patient's parameter values during the period of the data analysis, and to permit achievement of target therapeutic goals with maximum precision.
Course Co-coordinators:
Mario Eandi , M.D., Medical School University of Torino
Roger Jelliffe, M.D., Professor of Medicine, USC School of Medicine,
Director, USC Laboratory of Applied Pharmacokinetics
Faculty:
Nathalie Bleyzac, Pharm.D, Hospital Debrousse, Lyon, France
Nils Ove Hoem, Ph.D, School of Pharmacy, University of Oslo, Norway
Roger Jelliffe, M.D., Professor of Medicine, USC School of Medicine, Los Angeles, USA
Irina Bondareva, Ph.D., Laboratory of Mathematical Modelling, Institute of Physical and Chemical Medicine, Moscow Russia
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Day 1 - Basic Pharmacokinetics, Introduction to Population Modeling, and Clinical Applications
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9:00 AM - Welcome - Prof. M. Eandi
9:15 AM - Introduction to basic concepts in pharmacokinetics, including Review of Basic Pharmacokinetic Behavior. Drug Elimination and Renal Function - Dr. Jelliffe
9:30 AM - Evaluating Renal Function - Dr. Jelliffe
9:45 AM - Bayes' Theorem and the Bayesian Scenario of Planning, Monitoring, and Adjusting Drug Dosage for patients - Dr. Jelliffe
10:00 AM - Introduction to Population Modeling - Dr. Jelliffe
Why model? For description? For action? Traditional Data Fitting Methods Linear regression, NLLS, Bayesian
10:30 AM BREAK
10:45 AM - Parametric Population Models (Iterative 2 stage Bayesian, NONMEM )- Dr. Jelliffe
11:15 AM - Nonparametric Population models (NPML, NPEM) - Dr. Jelliffe
11:45 AM - Nonparametric Adaptive Grid (NPAG) Modeling - Dr. Jelliffe
12:30 PM - LUNCH
1:30 PM - Comparing Parametric and Nonparametric Approaches (IT2B, NPEM, NPAG) - Dr. Jelliffe
2:00 PM - Multiple Model (MM) Dosage Design for maximum precision regimens - Dr. Jelliffe
2:30 PM -Getting MM Bayesian Posterior Individual Parameter Distributions. The Interacting MM (IMM) Approach - Dr. Jelliffe.
3:00 PM - Introduction to the new Windows USC*PACK MM and IMM Clinical Program to Achieve Target Goals with Maximum Precision - Dr. Jelliffe
Demo - 1 compartment model Planning the Initial regimen - Gentamicin: CCr = 100, 50, 5.
3:15 PM - BREAK
3:30 PM - Entering past doses and levels, analysing the data. A patient on Gentamicin
An interesting patient on Tobramycin. - Dr. Jelliffe
4:00 PM - Hands on session - Dr. Jelliffe
The patient on Gentamicin. The interesting patient on Tobramycin.
4:30 PM - Demo - 2 compartment model Digoxin - Dr. Jelliffe
Setting the initial goals, planning the initial regimen
A simple patient with atrial fibrillation. Another interesting patient with atrial fib
5:00 PM - Hands on session - Setting the initial goals, planning the initial regimen.
The simpler patient with atrial fib
5:30 PM - Demo Vancomycin - Setting the initial goals, planning the initial regimen. - Dr. Jelliffe
5:45 PM - Hands on session - Setting the initial goals, planning the initial regimen.
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Day 2 - Intermediate Population Modeling
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9:00 AM - Optimizing drugs in neuropsychiatry - dr. Bondareva
9:30 AM - Individualization of Busulfan Therapy in Children for Bone Marrow Transplantation - Dr. Bleyzac
10:00 AM - Optimal procedures for population modeling - Dr. Jelliffe
First, determine the assay error pattern polynomial, to weight each data point properly
Second, use a parametric population model, get gamma, ranges
Third, use an NP population model, use gamma, ranges, get the entire parameter distribution.
10:30 AM - Demo - getting the assay error polynomial - Dr. Jelliffe
10:45 AM - Hands - on session - getting the assay error polynomial
11:00 AM - BREAK
11:15 AM - Demo - The IT2B program. Modelling Amikacin - Dr. Jelliffe
A typical patient data file: Running the program. Getting gamma, ranges, evaluating the results
11:45 AM - Hands-on session Modeling Amikacin
Running the program. Getting gamma, ranges, evaluating the results
12:30 - LUNCH
1:30 PM - Demo NPEM: Modeling Amikacin further. Using gamma, ranges results - Dr. Jelliffe
Evaluating the results - The log-likelihood function
Descriptors of dispersion : The DF50 and DF95
The 2 and 3-D plots of the marginal and joint marginal PDF's
2:15 PM - Hands-on session - NPEM: Amikacin. Using gamma, ranges - Dr. Jelliffe
Linking Nonparametric Models to the Multiple Model Adaptive Control Software
Deriving individual Bayesian posterior patient parameter joint densities
Evaluating relationships between parameters and covariates
3:00 PM - BREAK
3:15 PM - Optimal Times to Sample Serum Concentrations and other Responses - Dr. Jelliffe.
4:15 PM - Making Discrete "Nonparametric" Population Models from Literature Data - Dr. Jelliffe.
4:45 PM - Population PK/PD Modeling over the web - Dr. Jelliffe
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Day 3 - Advanced Population Modeling - Large and Nonlinear Models
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9:00 AM - Modeling Cyclosporine - Dr. Hoem
9:30 AM - Making large and nonlinear population models - Dr. Hoem
Demo - Using BOXES making a model of Cyclosporine
10:15 AM - Hands on session - Using BOXES making a model of Cyclosporine - Dr. Hoem
10:45 AM - BREAK
11:00 AM - Demo setting up Big IT2B Modelling Cyclosporine - Dr. Hoem
A typical subject data file
Setting up the model, the data, the instructions, sending it, analyzing it. Evaluating the results
11:30 AM - Hands-on session - setting up big IT2B - Modelling Cyclosporine.
Setting up the model, the data, sending it, analysing it, Evaluating the results
12:30 PM - LUNCH
1:30 PM - Demo Big NPEM Modelling Cyclosporine - Dr. Hoem
Setting up the model, the data, sending it, analyzing it, Evaluating the results
2:00 PM - Hands-on session - Big NPEM Modelling Cyclosporine
Setting up the model, the data, sending it, analyzing it, Evaluating the results
Prof. Mario Eandi MD mario.eandi@unito.it
Department of Anatomy and Pharmacology
Via P. Giuria 13
University of Torino - Italy
Organizing Secretary
Roberto Passera, PharmD roberto.passera@tin.it
Gian Paolo Zara MD gianpaolo.zara@unito.it
Phone: +39 011 6707803
Fax: +39 011 6707788
Admission to the Workshop: free – The number of the participants is limited to 30. The place is assigned on a first-come, first-served basis.
Registration to the Workshop: please send an e-mail or a Fax to the Organizing Secretary
Housing Information: Please contact
CO.AL.PI
Miss Silvia Pasquini
Phone +39 011 5613760
Fax +39 011 5621738
E-Mail: hotelres@hotelres.it