The Laboratory of Applied Pharmacokinetics of the University of Southern California School of Medicine and The Department of Clinical Pharmacology of the Medical University, St Petersburg, are pleased to announce a three-day workshop on
Tuesday - Thursday, May 14-16, 2002
Location: The St Petersburg Medical University, 197089, St Petersburg,
Tolstoj str., 6/8.
A registration form is available.
For more information, please contact
Irina Bondareva, Ph.D.
Laboratory of Mathematical Modelling
Research Institute of Physical and Chemical Medicine
4/6-b-101 Kuusinena Street
Moscow, 123 308, Russia
Phone: 7-(095)-195-3878
Fax: 7-(095)-314-1053
Email: ibondareva@mtu-net.ru
This course is intended for physicians, pharmacists and biomedical scientists with an interest in population pharmacokinetic / pharmacodynamic 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.
Faculty:
Prof. Zvartau E.E., St Petersburg Medical University
Roger W. Jelliffe, M.D., USC School of Medicine, Los Angeles, USA
Michael Pchelintsev, Ph. D., St Petersburg Medical University
Irina Bondareva, Ph.D., Research Institute of Physical and Chemical
Medicine, Moscow
Preliminary Program:
************************************************************
Day 1 - Basic Pharmacokinetics, Introduction to Population Modeling,
and Clinical Applications
************************************************************
8:30 AM - Registration
9:00 AM - Welcome Dr. Zvartau E.E.
9:15 AM - Introduction to basic concepts in pharmacokinetics, including
Review of Basic Pharmacokinetic Behavior.
Drug Elimination and Renal Function - Dr. Jelliffe
9:45 AM - Evaluating Renal Function Dr. Jelliffe
10:00 AM - Bayes' Theorem and the MAP Bayesian Scenario of Planning,
Monitoring, and Adjusting Drug Dosage for patients - Dr.
Jelliffe
10:15 AM - Introduction to Population Modeling - Dr. Jelliffe
Why model? For description? For action?
Types of PK models
Linear regression, NLLS, Bayesian
10:45 AM BREAK
11:00 AM - Parametric Population Models - Dr. Jelliffe
Iterative 2 stage Bayesian, NONMEM
11:30 AM - Nonparametric Population models - Dr. Jelliffe
NPEM, NPML
12:00 AM - Nonparametric Adaptive Grid (NPAG) Modeling - Dr.
Jelliffe
12:15 PM - LUNCH
1:15 PM - Comparing Parametric and Nonparametric Approaches - IT2B,
NPEM, and NPAG - Dr. Jelliffe.
1:45 PM - Multiple Model (MM) Dosage Design for maximum precision
regimens - Dr. Jelliffe
2:15 PM - Getting MM Bayesian Posterior Individual Parameter
Distributions. The Interacting MM (IMM) Approach - Dr.
Jelliffe.
2:45 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.
3:00 PM - BREAK
3:15 PM - Entering past doses and levels, analysing the data.
A patient on Gentamicin
An interesting patient on Tobramycin.
3:45 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
4:15 PM - Demo Vancomycin - Setting the initial goals, planning the
initial regimen. - Dr. Jelliffe
************************************************************
Day 2 - Intermediate Population Modeling
************************************************************
9:00 AM - Vancomycin Therapy Today - Dr. Jelliffe
9:30 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.
10:00 AM - Demo - getting the assay error polynomial - Dr. Jelliffe
10:30 AM - BREAK
10:45 AM - Demo - The IT2B program. Modelling Amikacin - Dr.
Jelliffe
A typical patient data file
Running the program. Getting gamma, ranges, evaluating
the results
11:15 AM - 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
Linking Nonparametric Models to the Multiple Model
Adaptive Control Software
Deriving individual Bayesian posterior patient parameter
joint densities
Evaluating relationships between parameters and covariates
12:00 Noon - LUNCH
1:00 PM - Optimal Times to Sample Serum Concentrations and other
Responses - Dr. Jelliffe.
1:45 PM - Making Discrete "Nonparametric" Population Models from
Literature Data - Dr. Jelliffe.
2:30 PM - BREAK
2:45 PM - Modeling of Antiepileptic Drugs - Dr. Bondareva
3:30 PM - Group discussion session
************************************************************
Day 3 - Advanced Population Modeling - Large and Nonlinear Models
************************************************************
9:00 AM - Population PK/PD Modeling over the web - Dr. Jelliffe
9:30 AM - Making large and nonlinear population models - Dr.
Bondareva
Demo - Using BOXES - making a Michaelis-Menten model of Phenytoin
10:30 AM - BREAK
10:45 AM - Demo setting up Big IT2B Modeling Phenytoin - Dr.
Bondareva
A typical subject data file
Setting up the model, the data, the instructions, sending it,
analysing it. Evaluating the results
12:30 PM - LUNCH
1:30 PM - Demo Big NPEM Modelling Phenytoin - Dr. Bondareva
Setting up the model, the data, sending it, analysing it,
Evaluating the results
3:00 PM - BREAK
3:15 PM -Group Review and Discussion.