The USC Laboratory of Applied Pharmacokinetics is pleased to announce
a 1 Day workshop

Principles of Pharmacokinetics -
New Unified Approaches to Parametric and Nonparametric Population PK and PD Modeling - Applications to Therapeutic Drug Monitoring and to Optimal individualization of Drug Therapy and cancer chemotherapy.

January 23, 2003

Location -
Auspices - 2003 Western Multiconference on Computer Modeling and Simulation
INTERNATIONAL CONFERENCE ON HEALTH SCIENCES SIMULATION
Orlando Airport Marriott, Orlando, Florida

Registration information may be found at
http://www.scs.org/regform.pdf

This course is intended for biomedical scientists, physicians, pharmacists and those with an interest in drug development and evaluation, medical decision making, clinical trials, population pharmacokinetic / pharmacodynamic modeling and simulation, and therapeutic drug monitoring and individualization of drug therapy for optimally precise patient care.

The course will examine and review current and new methods of parametric and nonparametric population PK/PD modeling, with special emphasis on the FOCE parametric Iterative 2 Stage Bayesian (IT2B) and the nonparametric adaptive grid (NPAG) programs. Statistical and mathematical consistency and efficiency of methods in population PK/PD modeling will be discussed, evaluated, and compared.

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 "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. Such changes take place in patients not only when they are acutely ill and highly unstable, but also in children as they grow and mature, and therapy much be guided during all this time. In addition, changes also take place with varying compliance, and a changing apparent volume of distribution may well be a clue to good or poor compliance in a patient.

Faculty

Roger W. Jelliffe, M.D., Professor of Medicine, USC, Course coordinator.

Preliminary Program

Morning session Basic Pharmacokinetics, Introduction to Population Modeling 

8:30 AM - Registration
9:00 AM - Welcome : Dr. Jelliffe
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  and Creatinine clearance in unstable patients
9:45 AM - Bayes' Theorem and the Bayesian Scenario of Planning, Monitoring, and 
          Adjusting Drug Dosage for patients 
10:00 AM- Introduction to Population Modeling -
	  Determining the assay error polynomial - 
	  Parametric Models -  Iterative 2 stage Bayesian 
	  Nonparametric models - NPEM, NPML, NPAG

10:30 AM BREAK

10:45 AM- Demo - The IT2B program.  Modeling 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. 
	  Evaluating the results - The log-likelihood function
	  The 2 and 3-D plots of the marginal and joint marginal PDF's
11:45 AM- Comparing Parametric and Nonparametric Approaches - IT2B, NPEM, and NPAG
	  Their statistical consistency and efficiency. Their results.
12:00   - Optimal Times to Sample Serum Concentrations and other Responses 

12:30 PM- LUNCH


Afternoon Session Clinical Applications 

1:30 PM - Outcome Analysis of Individualized Digoxin, Lidocaine, Busulfan 
	  and Aminoglycoside Therapy 
1:45 PM - Multiple Model (MM) Dosage Design for maximum precision dosage 
	  regimens
2:15 PM - Demo - Clinical Applications - A patient on Gentamicin, an 
	  interesting patient on Tobramycin
2:45 PM - Demo - Vancomycin - Setting the initial goals, planning the 
	  initial regimen.

3:00 PM - BREAK

3:15 PM - Demo - Digoxin. The Reuning population model.
	  Setting goals in the peripheral compartment
	  Two interesting patients with atrial fiibrillation.
3:45 PM - The digoxin - quinidine interaction - pharmacokinetic implications 
	  for transplant and cancer chemotherapy.
4:15 PM - New Models of Cyclosporine
4:45 PM - Review and discussion
5:15 PM - Adjourn