The USC Laboratory of Applied Pharmacokinetics and the Schools of Medicine and Pharmacy, and the School of Pharmacy, University of Navarra, Spain, 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

Thursday - Saturday, January 24-26, 2002.
Location: The University of Navarra, Pamplona, Spain.

A registration form is available.

For more information, please contact

Azucena Aldaz, Pharm. D.
Servicio de Farmacia, Facultad de Medicina,
Clinica Universidad de Navarra
Avda Pio XII, n 36
31008 Pamplona, Spain

Phone: 34-948-296-692, x4113, 4119
Fax: 34-948-175-278
Email: aaldaz@unav.es

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.

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Course Co-coordinators:

Azucena Aldaz, Ph.D., Faculty of Pharmacy, University of Navarra
Roger W. Jelliffe, M.D., Professor of Medicine, USC School of Medicine, 
        Director, USC Laboratory of Applied Pharmacokinetics.
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Faculty:

Nathalie Bleyzac, Pharm.D, Hospital Debrousse, Lyon, France
Aida Bustad, B.A.,USC Laboratory of Applied Pharmacokinetics
George Drusano, M.D., Albany Medical College, Albany, NY, USA
Nils Hoem, Ph.D, School of Pharmacy, University of Oslo, Norway 
Roger W. Jelliffe, M.D., Professor of Medicine, USC School of Medicine, 
Guest speakers from Valencia


Preliminary Program:

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Day 1 - Basic Pharmacokinetics, Introduction to Population Modeling, 
and Clinical Applications
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8:30 AM - Registration
9:00 AM - Welcome Dr. Aldaz
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 - Dr. Jelliffe
        		 Iterative 2 stage Bayesian, NONMEM
11:15 AM - Nonparametric Population models - Dr. Jelliffe
         		NPML, NPEM
11:45 AM - Nonparametric Adaptive Grid (NPAG) Modeling - 
        Dr. Jelliffe

12:15 PM - LUNCH

1:15  PM - Comparing Parametric and Nonparametric Approaches - IT2B, 
NPEM, and NPAG - Ms. Aida Bustad.
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 - Hands  on session - Dr. Jelliffe
		The patient on Gentamicin
		The interesting patient on Tobramycin.
4:15 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
4:45 PM - Hands  on session - Setting the initial goals, planning the 
		initial regimen.
		The simpler patient with atrial fib
5:15 PM - Demo  Vancomycin - Setting the initial goals, planning the 
		initial regimen. - Dr. Jelliffe
5:30 PM - Hands  on session - Setting the initial goals, planning the 
		initial regimen.

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Day 2 - Intermediate Population Modeling
************************************************************
8:30   AM - Antiviral Therapy Today - Dr. Drusano
9:00 AM - Individualization of Busulfan Therapy in Children for Bone 
Marrow Transplantation - Dr. Bleyzac
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
10:15 AM - Hands - on session - getting the assay error polynomial

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 - Hands-on session  Modeling Amikacin
Running the program. Getting gamma, ranges, evaluating 
the results

12:00 Noon - LUNCH

1:00 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
1:45 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

2:30 PM - BREAK

2:45 PM - Optimal Times to Sample Serum Concentrations and other 
Responses - Dr. Jelliffe.
3:15 PM - Topic to be Announced - Guest speaker from Valencia
3:45 PM - Making Discrete "Nonparametric" Population Models from 
Literature Data - Dr. Jelliffe.
4:15 PM - Population PK/PD Modeling over the web - Dr. Jelliffe

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Day 3 - Advanced Population Modeling - Large and Nonlinear Models
************************************************************
8:30 AM - Modelling Cyclosporine - Dr. Hoem
9:00 AM - Making large and nonlinear population models - Dr. Jelliffe
Demo - Using BOXES  making a model of Cyclosporine
10:00 AM - Hands  on session - Using BOXES  making a model of 
Cyclosporine - Dr. Jelliffe

10:30 AM - BREAK

10:45 AM - Demo  setting up Big IT2B  Modelling Cyclosporine - Dr. 
Jelliffe
         		A typical subject data file
Setting up the model, the data, the instructions, sending it, 
analyzing it. Evaluating the results
11:15 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. Jelliffe
		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

3:00 PM - BREAK

3:15 PM - Topic to be Announced - Guest speaker from Valencia 
3:45 PM - Topic to be Announced - Guest speaker from Valencia 
4:30 PM - Group Discussion and Certificate Presentation.