Roger Jelliffe jelliffe at
Thu Dec 14 02:48:37 EST 1995

                                                November 28, 1995

Dear Colleague:

        The Laboratory of Applied Pharmacokinetics of the University
of Southern California School of Medicine is putting on another
satellite pharmacokinetic conference. It is on "Population PK/PD
Modeling, Optimal TDM, Individualized Drug Therapy, and 'Multiple
Model' Design of Drug Dosage". Emphasis is on research and clinical
aspects of Population Modeling, and then on clinical applications.
Sponsorship is being sought from the American and the International
Medical Informatics Associations (AMIA and IMIA). Postgraduate
education credit for pharmacists is being sought from the USC School
of Pharmacy.

WHERE?  WHEN?  The conference will be held in the Conference Room of
the USC School of Pharmacy, and the Basement Computer Classroom of
the USC School of Pharmacy, on Friday and Saturday, February 23 and
24, respectively.  One must arrange travel, hotel, and meal
accommodations independently.  Further information about local hotels,
maps, etc. will be sent when we confirm your registration.

        The conference is intended to increase the understanding of
Population Pharmacokinetic Modeling and its role in optimization of
clinical trials and practical drug therapy. The concepts and software
to implement them (the parametric USC*PACK clinical and the iterative
Bayesian and nonparametric NPEM2 programs) are intended for general
use, with special application to the optimal modeling of drugs used
in cardiovascular and infectious disease, AIDS, cancer, transplants,
psychiatric illnesses, and for Phase 1-2 and 2-3 trials and
concentration-controlled clinical trials. Information obtained in this
conference can also be implemented on other software.

WHO IS IT FOR?  The conference is for physicians and pharmacists with
a working knowledge of pharmacokinetics (Vd, Kel, etc) to apply modern
parametric and nonparametric modeling concepts to the study of population
models. Methods to describe diffusion of antibiotics into simulated
endocardial vegetations and to compute and plot bacterial killing curves
and post-antibiotic effects will also be discussed.  New "Multiple Model"
(MM) approaches to dosage regimens will be introduced. Applications to
Trimethoprim, Aminoglycosides, Vancomycin, Digoxin, and other drugs will
be discussed.

BRING YOUR NOTEBOOK!  For those of you who already have or who wish to
obtain the relevant clinical software for the purposes to which this
workshop is devoted, and who wish to bring it in your  own laptop or
notebook computer to the workshop, you are invited to do your own hands
on with it on your own machines.

OBJECTIVES:  After the conference, participants should be able to: 1) Define
the concepts behind parametric and nonparametric population modeling,
2) Understand the iterative Bayesian and nonparametric  NPEM2 population
modeling programs, 3) Implement population modeling and Bayesian adaptive
control methods to introduce a new drug to the marketplace with optimal
strategies for its precise and safe use, 4) Compute bacterial growth and
killing curves, post-antibiotic effects, and drug diffusion into endocardial
vegetations, and 5) Understand the application of Bayesian Adaptive Control
concepts to practical aspects of managing drug therapy optimally for patients.

THE FACULTY are: Roger Jelliffe, M.D., Prof. of Medicine, USC School of
Medicine, Course Coordinator, David Bayard, Ph.D., Senior Scientist, Guidance
and Control Section, Jet Propulsion Laboratory, Pasadena, CA, Agneta Hurst,
Pharm.D., Assistant Professor of Clinical Pharmacy, USC School of Pharmacy,
George Jaresko, Pharm.D., Assistant Professor of Clinical Pharmacy, USC School
of Pharmacy, Pascal Maire, Pharm.D, Hospital Antoine Charial, Lyon, France,
Mark Milman, Ph.D., Senior Scientist, Guidance and Control Section, Jet
Propulsion Laboratory, Pasadena, CA, Alan Schumitzky, Ph.D., Prof. of
Mathematics, USC, and Michael Van Guilder, Ph.D., Lecturer in Mathematics,
Cal-State University, Fullerton.

        Please call (213) 342-1300, Fax us at (213) 342-1302, or Email us at
jelliffe at if you have any questions.


                                                Roger W. Jelliffe, M.D.
                                                Professor of Medicine

Preliminary Program: "Population PK/PD Modeling, Optimal TDM, Individualized
Drug Therapy, and New 'Multiple Model' Design of Drug Dosage"

Day 1 - Friday, February 23, 1996

8:30 AM - Registration
9:00 AM - Welcome - Dr. Roger Jelliffe
9:05 AM - An Overview of Population Modeling - Dr. Jelliffe
9:15 AM - Linear and Nonlinear Models - Dr. Jelliffe
                PK Models, Diffusion Models, Effect Models
                Cell and Bacterial Growth and Kill Models
9:45 AM - Parametric Population Models - Dr. Jelliffe
10:15 AM - Nonparametric Population Models - Dr. Jelliffe
                NP Maximum Likelihood
                NP Expectation - Maximization
                Their Relationship to the Separation Principle and to Optimal
                        Drug Regimens

10:45 AM - Break

11:00 AM - Parameterizing Population Models - Dr. Jelliffe
                Linking Parameters to Descriptors
                        Body Weight, Ideal Body Weight, and Body Mass Index
                        Creatinine Clearance
                        Cardiac Output
11:30 AM - Clinical and Research Issues in Population Modeling - Dr. Jelliffe
                Evaluating Renal Function
                Determining the Assay Error Pattern and the Weighting Scheme
                        for Measurements
                When to Get Serum Levels: Optimal Sampling Schedules
                Modeling Environmental Errors in Dosage Preparation and

12:30 PM - Lunch

1:30 PM - Foundations of Nonparametric Population Modeling - Dr. Schumitzky
2:10 PM - "Multiple Model" Adaptive Control and Optimal Drug Dosing - Dr.
2:45 PM - "Maximum Entropy Population Models" - Dr. Milman

3:15 PM - Break

3:30 PM - Clinical Models of Drug Diffusion - Dr. Maire
4:00 PM - Modeling Bacterial Growth and Kill, and the Post-Antibiotic effect -
                        Dr. Maire
4:20 PM - Modeling Pharmacologic Effects and Drug Binding to Effect Sites -
                        Dr. Maire
4:40 PM - Once Daily Aminoglycoside Therapy - Pros and Cons - Dr. Jelliffe
                Evaluating 80 q 8 versus 240 q 24 - 2 cases, 3 values of CCr
                Serum AUC, and AUC in a peripheral effect compartment
                Evaluating the relative benefit of nonlinear uptake
                General Discussion
5:30 PM - Adjourn

An Evening Get - Together at the USC Medical Faculty Center
        6:00 PM -       No - Host Bar
        6:30 PM -       Dinner
        7:15 PM -       "Clinical Studies with Multiple Model Dosage Regimens
                        of Amikacin - Preliminary Results" - Dr. Maire

Day 2 - Saturday, February 24, 1996
9:00 AM - Making a Population Model of Amikacin with NPEM2 - Dr. Jelliffe
9:15 AM - The Front part - an Iterative Bayesian Population Modeler -
                        Drs. Jelliffe, Hurst, Jaresko, Maire, and Van Guilder
                Selecting patient data file types
                Evaluating Bioavailability
                Entering the Assay Error Pattern Polynomial
                Selecting the Convergence Criterion and iterations
                Defining the first Bayesian prior
                Defining the ranges to pass to the nonparametric back part
9:45 AM - The Back part - the Nonparametric Population Modeler itself -
                        Drs. Jelliffe, Hurst, Jaresko, Maire, and Van Guilder
                Using the program the standard way - picking up data and
                        ranges from the front part
                Selecting the number of grid points for the joint probability
                        density function (PDF)
                Evaluating the Nonparametric Output
                        The log-likelihood function
                        The difference between a cycle likelihood and the max
                        The means, modes, skewnesses, kurtoses, and the
                        New Descriptors of Dispersion - the DF-50 and DF-95
                        The 2-D plots of the Marginal PDF's
                        The 3-D plots of pairs of Joint Marginal PDF's
                               Comparing these with covariances and correlations
                        Summarizing the grid points and their probabilities
                        Linking Nonparametric models to Multiple Model Adaptive
                        Evaluating the convergence - Absolute and normalized
                                convergence plots
10:30 AM - Break

10:45 AM - More Population Modeling - Drs. Jelliffe, Hurst, Jaresko, Maire,
                        and Van Guilder
                The Front part - seeing the output, parameter files, and
                        scatter plots
                The Back Nonparametric part - seeing the output, parameter
                        files, and scatter plots
11:15 AM - Running the modeler without the front part - Dr. Jelliffe
                Recovering and continuing after a power failure, or continuing
                        a previous run
                Plotting results of a previous run

12:00 Noon - Lunch

1:00 PM - Clinical Applications: Gentamicin  - Dr. Jaresko
1:30 PM - Clinical Applications: Digoxin - Dr. Jelliffe
                Planning the initial regimen. Controlling the Peripheral
                An interesting patient with Atrial Fibrillation
                A patient with very high levels - why? Digoxin - like
                        material or the dig-quinidine interaction?
2:00 PM - Clinical Applications: Vancomycin - Dr. Hurst
                Setting the trough goals. Planning the initial regimen
2:30 PM - Clinical Applications: Trimethoprim - Dr. Jelliffe
                Setting the goals for PCP pneumonia

3:00 PM Break

3:15 PM - Clinical Applications: Gentamicin - Dr. Jelliffe
                Goals versus format
                Modeling diffusion into vegetations or abscesses
                Modeling post - antibiotic effect and bacterial growth
                        and kill
                Effect models - occupation of toxic binding sites
3:45 PM - Clinical Applications: Lidocaine - Dr. Jelliffe
                Setting the serum goals: Planning the tapering infusion
4:15 PM - Clinical Applications: Theophylline - Dr. Jelliffe
                Setting the goals and planning the regimen: regular and
                        sustained release forms

4:45 PM - Adjourn

Registration Form

        I wish to register to attend the USC - AMIA - IMIA Symposium on
"Population PK/PD Modeling, Optimal TDM, Individualized Drug Therapy, and
New 'Multiple Model' Design of Drug Dosage"  on February 23 and 24, 1996.

($250.00. For members of  AMIA or IMIA, only $210.00)

                Get - Together Dinner Friday evening_______________$40.00

                I will______    will not_____  attend the dinner on Friday

                Total: registration plus dinner if selected:    $____________

                (Sorry - we cannot handle credit cards or purchase orders. We
                can handle checks and foreign travelers checks in US dollars.)

                Please make checks payable to the:

                        Laboratory of Applied Pharmacokinetics

                Name of Registrant ______________________________




                City, State, Zip_______________________________      _____


                Phone (____)________________Fax (____)_________________


                I am______ am not_______ a member of AMIA.
                I am______ am not_______ a member of IMIA.

                Please return this form, with your check, directly to:

                Roger W. Jelliffe, M.D.
                Laboratory of Applied Pharmacokinetics
                USC School of Medicine
                CSC 134-B
                2250 Alcazar Street
                Los Angeles, CA 90033

        Our phone is (213) 342-1300, and our Fax is (213) 342-1302.

        Note:  Please register early. First come are first served. Registration
is limited to the available spaces available. Cancellations must be made at
least 10 days before the workshop in order to obtain a refund.
        I would _____ would not _____ also like to receive information about
the USC software.
        I heard about this conference from______mailing  _____word of mouth
          _____electronic bulletin board  _____other (please specify)_________

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