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Object Oriented PKPD Modeling
13th International Congress of
Therapeutic Drug Monitoring & Clinical Toxicology
Salt Lake C...
CONTENTS
• Object Orientation
– Lego Metaphor
– PKPD Objects
• PKPD Object Library
• Case Studies
– Mycophenolic Acid (PK ...
OBJECT ORIENTATION
Window Object Door Object
Roof
Objects
Brick
Objects
Desktop
Lego Metaphor
OBJECT ORIENTATION
Lego 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
TPe...
CASE STUDY: MYCOPHENOLIC ACID
MPAG Renal
Elimination
(70%)
MPA Metabolic
Elimination (100%)
MPA Renal
Elimination (0%)
MPA...
CASE STUDY: MYCOPHENOLIC ACID
Food intake
Enterohepatic Circulation
CASE STUDY: TOLBUTAMIDE
Insulin Minimal Model
Glucose Minimal Model
1) Stimulates insulin release
2) Increases glucose sen...
CASE STUDY: TOLBUTAMIDE
Glucose
Challenge
(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 ...
CONCLUSIONS
• Object oriented PKPD modeling (OOPKPD) is an innovative
method applicable to a broad range of modeling probl...
Thank you for your attention.
Any Questions?
CONTACT
www.mediware.cz
george.dousa@mediware.cz
jiri.potucek@mediware.cz
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Salt Lake City 2013 - Presentation

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13th International Congress of Therapeutic Drug Monitoring & Clinical Toxicology, Salt Lake City, USA, September 22-26, 2013

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Salt Lake City 2013 - Presentation

  1. 1. 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
  2. 2. CONTENTS • Object Orientation – Lego Metaphor – PKPD Objects • PKPD Object Library • Case Studies – Mycophenolic Acid (PK model) – Tolbutamide (PKPD model) • Software Implementation – Edsim++ – MwPharm++ • Conclusions
  3. 3. OBJECT ORIENTATION Window Object Door Object Roof Objects Brick Objects Desktop Lego Metaphor
  4. 4. OBJECT ORIENTATION Lego Model
  5. 5. OBJECT ORIENTATION Compartment Input Output Transfer Effect Tool Patient PKPD Objects
  6. 6. 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
  7. 7. CASE STUDY: MYCOPHENOLIC ACID MPAG Renal Elimination (70%) MPA Metabolic Elimination (100%) MPA Renal Elimination (0%) MPA Absorption MPA Distribution MPAG Bile Accumulation (30%) MPAG Bile Excretion
  8. 8. CASE STUDY: MYCOPHENOLIC ACID Food intake Enterohepatic Circulation
  9. 9. CASE STUDY: TOLBUTAMIDE Insulin Minimal Model Glucose Minimal Model 1) Stimulates insulin release 2) Increases glucose sensitivity ß-cells 1) Stimulates cellular glucose uptake 2) Simulates glycogen synthesis Oral Glucose Challenge (75 g) Oral Tolbutamide (1 g) Subcutaneous Insulin (0 IE)
  10. 10. CASE STUDY: TOLBUTAMIDE Glucose Challenge (75 g) Tolbutamide (1 g) Insulin Response
  11. 11. SOFTWARE IMPLEMENTATION EDSIM++ Model Designer MWPHARM++ Model User MODEL XML TDMPKPD
  12. 12. 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
  13. 13. 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).
  14. 14. Thank you for your attention. Any Questions?
  15. 15. CONTACT www.mediware.cz george.dousa@mediware.cz jiri.potucek@mediware.cz

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