Salt Lake City 2013 - Presentation

Object Oriented PKPD Modeling

13th International Congress of

Therapeutic Drug Monitoring & Clinical Toxicology

Salt Lake City, USA, September 22-26, 2013

Ing. Jiří Douša, 3rd Medical Faculty Charles University, Prague, Czech Republic

Funded by the EU

CONTENTS

• Object Orientation– Lego Metaphor– PKPD Objects

• PKPD Object Library

• Case Studies– Mycophenolic Acid (PK model)– Tolbutamide (PKPD model)

• Software Implementation– Edsim++– MwPharm++

• Conclusions

OBJECT ORIENTATION

Window Object Door Object

Roof Objects

Brick Objects

Desktop

Lego Metaphor

OBJECT ORIENTATIONLego Model

OBJECT ORIENTATION

Compartment Input Output

Transfer Effect Tool Patient

PKPD Objects

PKPD OBJECT LIBRARY°

Compartment Transfer Input Output Effect

TCompartment TTransport TInjection TElimination TSigmoid

TPeripheral TDistribution TInfusion TTransformation TResponse

TSink TEnzymatic TAbsorption TVirtualElim TKillStatic

TPortal TTransit TWeibull THemoDialysis TKillAdaptive

TVirtual TLink TGamma TPeriDialysis TKillMic

TVirtualLinked TExcretion TAntagonism*

XInsulin TMetabolism TSynergism*

XGlucose TInhibition*

TCompetition*

*Interaction objects °Tools not listed.

Interactions

PK PD

CASE STUDY: MYCOPHENOLIC ACID

MPAG Renal Elimination(70%)

MPA MetabolicElimination (100%)

MPA Renal Elimination (0%)

MPAAbsorption

MPADistribution

MPAG BileAccumulation(30%)

MPAG BileExcretion

CASE STUDY: MYCOPHENOLIC ACID

Food intake

Enterohepatic Circulation

CASE STUDY: TOLBUTAMIDE

Insulin Minimal Model

Glucose Minimal Model

1) Stimulates insulin release2) Increases glucose sensitivity ß-cells

1) Stimulates cellular glucose uptake2) Simulates glycogen synthesis

Oral Glucose Challenge (75 g)

Oral Tolbutamide (1 g)

Subcutaneous Insulin (0 IE)

CASE STUDY: TOLBUTAMIDE

GlucoseChallenge(75 g)

Tolbutamide (1 g)

Insulin Response

SOFTWARE IMPLEMENTATION

EDSIM++

Model Designer

MWPHARM++

Model User

MODEL XML

TDMPKPD

APPLICATION COOPERATION

Edsim++ MwPharm++°

Mission

Environment

Workflow

Subject

° Ranked number 1 in a review by Fuchs et al. (Clin Pharmacokinet (2013) 52:9–22)

PKPD Modeling• Simulation• Population analysis

TDM Process• Dose Calculation• Patient analysis

Education, Research Hospital, Clinic

Creative, Exploratory Routine, Standards

Population Individual

CONCLUSIONS

• Object oriented PKPD modeling (OOPKPD) is an innovative method applicable to a broad range of modeling problems.

• OOPKPD is implemented in the user-friendly software package Edsim++, which can be used in research and education.

• The Edsim++ OOPKPD modeling engine can be used by other applications using a software development kit (SDK).

• Edsim++ can share PKPD models with MwPharm++, enabling the use of advanced PKPD models in routine TDM.

• MwPharm was ranked as the number one TDM software package in a review by Fuchs et al. (2013).

Thank you for your attention.

Any Questions?

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