WCDA - PKPD Workshop

PK/PD - General Concepts
and Advanced Material - ADVANCED LEVEL

PK/PD Modeling Methods and Clinical Applications (Intermediate - Advanced - Expert Level)

Faculty:

Roger Jelliffe, MD
Irina Bondareva, Ph.D.
George Drusano, MD
Rüdiger Port, MD
Alexander Vinks, Ph.D.

Target Participants:

This workshop, using minimal math, starts at a beginning level and progresses to an advanced level over 2 intensive days. It is intended for physicians, pharmacists, clinical chemists and biomedical scientists who have an interest in clinical therapeutic drug monitoring and optimal individualization of drug therapy for patient care and in population pharmacokinetic and pharmacodynamic research modeling techniques. Participants will be introduced to the USC*PACK software which can be used both for therapeutic drug monitoring as well as for parametric and nonparametric population PK/PD and physiological modeling.

Objectives and Expectations:

After this workshop, the participant should:

1.	Be able to describe basic pharmacokinetic behavior of drugs in patients.
2.	Be able to design optimal initial individualized dosage regimens of drugs to hit selected target goals most precisely.
3.	Be able to enter and store patient data of doses, TDM serum concentrations, etc., and to make an individualized model of drug behavior in that patient.
4.	Be able to develop an adjusted dosage regimen based on the patient's individualized model.
5.	Understand how to apply these techniques to therapy with vancomycin, digoxin, anticonvulsants, and drugs for AIDS, cancer, and transplants.
6.	Understand the basic ideas (not the math) behind parametric and nonparametric population PK/PD modeling.
7.	Know how to determine the error polynomial for a drug assay, to fit each data point by an optimal measure of its credibility.
8.	Understand Monte-Carlo simulation and its applications to clinical situations.
9.	Understand the basic concepts of multiple model dosage design.

PK/PD Modeling Methods and Clinical Applications (Intermediate - Advanced - Expert Level)

Tuesday,
September 07th, 2004

Preliminary Program

Time	Topic
8:30	Beginning-Intermediate Clinical PK 1 The basic PK model – Roger Jelliffe Its parameters: Ka, Kel, Vol, Clearance, Kcp, Kpc, T1/2 Dose individualization using target concentration strategy An example for discussion: tracking drug behavior in unstable patients, with changing doses, changing renal function, and ad-lib serum samples. Basic PK building blocks Evaluating renal function, especially in unstable patients Evaluating lab assay errors, and then acting on them! Evaluating other environmental errors
9:30	Beginning-Intermediate Clinical PK 2 Ways of fitting data - Roger Jelliffe Linear regression on logs of data Weighted nonlinear least squares Maximum Aposteriori Probability (MAP) Bayesian fitting The basic MAP Bayesian scenario When to get data best - Alexander Vinks
10:30	Coffee
11:00	Beginning-Intermediate Population Modeling Parametric, iterative 2 stage Bayesian (IT2B) population modeling - Roger Jelliffe Strengths and weaknesses of parametric models
11:45	Nonparametric Population Modeling - Roger Jelliffe Its strengths and weaknesses Unified approaches to population modeling
12:30	Multiple Model Dosage Design - Roger Jelliffe
13:00	Lunch
14:30	Intermediate PK – Tissue Distribution Modeling diffusion in endocardial vegetations - Roger Jelliffe Modeling bacterial growth and kill, and post-antibiotic effect
15:30	How to describe and build PD relationships for anti-infective drugs - George Drusano
16:00	Erythropoetin therapy in childhood renal anemia - Rüdiger Port
16:30	End

PK/PD Modeling Methods and Clinical Applications (Intermediate - Advanced - Expert Level)

Wednesday,
September 08th, 2004

Preliminary Program

Time	Topic
8:30	Advanced PK 3 Modeling linear and nonlinear antiepileptic drug models - Irina Bondareva
9:00	Outcome and costs of a goal-oriented, model-based, active TDM service – Alexander Vinks
9:45	Combination chemotherapy - Monte-Carlo simulation: from PK/PD Relationships to clinical applications - George Drusano
10:30	Coffee
11:00	Applied Clinical PK 4 Getting Nonparametric Bayesian Posteriors – Roger Jelliffe Multiple Model (MM) versions Interacting Multiple Model (IMM) versions for very unstable patients The structure of MM Bayesian dosage individualization and adjustment
12:00	Aminoglycoside ototoxicity - Roger Jelliffe
12:30	Introduction to Clinical Cases - Roger Jelliffe Planning initial MM aminoglycoside therapy Normal and reduced renal function
13:00	Lunch
14:30	Advanced Clinical PK 5 More clinical case histories - Roger Jelliffe Planning initial vancomycin therapy Planning initial digoxin therapy A gentamicin patient with changing renal function A tobramycin patient with changing renal function and changing clinical status Digoxin and atrial fibrillation Why the literature says it is no good for conversion Why the literature is probably wrong Four interesting digoxin cases
16:30	End

Link to the PK/PD General Concepts program at the beginner - intermediate level

Beginning-Intermediate Clinical PK 1

Beginning-Intermediate Clinical PK 2

Nonparametric Population Modeling - Roger Jelliffe

Multiple Model Dosage Design - Roger Jelliffe

Intermediate PK – Tissue Distribution

How to describe and build PD relationships for anti-infective drugs - George Drusano

Advanced PK 3

Introduction to Clinical Cases - Roger Jelliffe