Post on 16-Jul-2015
transcript
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?
CONTACT
www.mediware.cz
george.dousa@mediware.cz
jiri.potucek@mediware.cz