Beginners – intermediate pk / pd general concepts workshop program

World Conference on Dosing of Antiinfectives Pre-Conference Workshop Program September 06-11, 2004 PK/PD - General Concepts and Advanced Material
Workshop on September 07-08, 2004
PK / PD General Concepts Workshop Program (Beginner – Intermediate Level)
Tuesday, September 07th, 2004

Time Topic
PK 1 Basic Principles - Michael Weiss
Structure of the body, administration and sampling sites Transport processes Clearance, volume of distribution, half-life PD 1 Ligand Binding and Receptors - Nick Holford
Receptors and binding sites Specific binding and non-saturable binding Occupancy, stimulus and response models PK 2 Processes - Michael Weiss
Hepatic and renal elimination
Absorption and bioavailability
Plasma protein and tissue binding
PD 2 Immediate Drug Effects - Nick Holford
The Emax and Sigmoid Emax models of drug action Time course of drug effect Duration of drug effect PK 3 Data Analysis I - Michael Weiss
Compartmental and noncompartmental models Population Data Analysis - Nick Holford
Individual vs population methods Why understanding fixed and random effects is important Sources of PK and PD variability Common Parallel Session – Discussion (PK and PD) by
Nick Holford & Michael Weiss
File name: WCDA_Workshop_PKPD_Program.doc World Conference on Dosing of Antiinfectives Pre-Conference Workshop Program September 06-11, 2004 PK / PD General Concepts Workshop Program (Beginner – Intermediate Level)
Wednesday, September 08th, 2004

Time Topic
PK / PD General Concepts
Advanced PK 4 - Michael Weiss
Multiple dosing Designing dose regimens Nonlinear PK PD 3 Delayed Drug Effects - Nick Holford
Distribution delay and the effect compartment Physiological delay and the turnover model family Thiopentone, digoxin, warfarin, anti-depressants Advanced PK 5 Data Analysis II -
Michael Weiss
PD 4 Exposure Response - Nick Holford
What does exposure mean? Cumulative effects and schedule dependence Diuretics and anti-cancer agents PK / PD General Concepts Workshop
Physiologically Based PK - Michael Weiss
Recirculatory modeling (initial distribution) PK in isolated organs and destructive sampling Allometric up-scaling Clinical Pharmacology = Disease Progression + Drug Action
Nick Holford
Introduction to the concepts of disease progression modeling Application to clinical pharmacology and drug development Alzheimer's disease and Parkinson's disease Applications in Anticancer Drug Therapy
Charlotte Kloft, Berlin:
Pharmacokinetics of high-molecular anticancer agents
Ulrich Jaehde, Bonn:
Surrogate parameters in cancer chemotherapy
Rüdiger Port, Heidelberg:
Tissue pharmacokinetics with non-invasive measurements File name: WCDA_Workshop_PKPD_Program.doc World Conference on Dosing of Antiinfectives Pre-Conference Workshop Program September 06-11, 2004 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. Be able to design optimal initial individualized dosage regimens of drugs to hit selected target goals most precisely. 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. Be able to develop an adjusted dosage regimen based on the patient's individualized model. Understand how to apply these techniques to therapy with Vancomycin, Digoxin, anticonvulsants, and drugs for AIDS, cancer, and transplants. Understand the basic ideas (not the math) behind parametric and nonparametric population PK/PD modeling. Know how to determine the error polynomial for a drug assay, to fit each data point by an optimal measure of its credibility. Understand Monte-Carlo simulation and its applications to clinical situations. Understand the basic concepts of multiple model dosage design. File name: WCDA_Workshop_PKPD_Program.doc World Conference on Dosing of Antiinfectives Pre-Conference Workshop Program September 06-11, 2004 PK/PD Modeling Methods and Clinical Applications (Intermediate – Advanced – Expert Level)
Tuesday, September 07th, 2004
Time Topic
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. Evaluating renal function, especially in unstable patients Evaluating lab assay errors, and then acting on them! Evaluating other environmental errors 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
Beginning-Intermediate Population Modeling
Parametric, iterative 2 stage Bayesian (IT2B) population modeling - Roger Jelliffe
Strengths and weaknesses of parametric models
Nonparametric Population Modeling - Roger Jelliffe
Its strengths and weaknesses Unified approaches to population modeling Multiple Model Dosage Design - Roger Jelliffe
Intermediate PK – Tissue Distribution
Modeling diffusion in endocardial vegetations - Roger Jelliffe
Modeling bacterial growth and kill, and post-antibiotic effect
How to describe and build PD relationships for anti-infective drugs - George Drusano
Erythropoetin therapy in childhood renal anemia - Rüdiger Port
File name: WCDA_Workshop_PKPD_Program.doc World Conference on Dosing of Antiinfectives Pre-Conference Workshop Program September 06-11, 2004 PK/PD Modeling Methods and Clinical Applications (Intermediate – Advanced – Expert Level) Wednesday, September 07th, 2004
Time Topic
Advanced PK 3
Modeling linear and nonlinear antiepileptic drug models - Irina Bondareva
Outcome and costs of a goal-oriented, model-based, active TDM service –
Alexander Vinks
Combination chemotherapy - Monte-Carlo simulation: from PK/PD Relationships to clinical applications - George Drusano
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 Aminoglycoside ototoxicity - Roger Jelliffe
Introduction to Clinical Cases - Roger Jelliffe
Planning initial MM aminoglycoside therapy 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 File name: WCDA_Workshop_PKPD_Program.doc

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