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Pharmacometric Model Test on Theory of “Multi-components taking effect together” in Compound TCM (CDDP for example). Reporter: Qingjing Liu Supervisor: Professor Henry Sun 16 April 2012. Outline. Background Objective Contents and Methods - PowerPoint PPT Presentation
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Reporter: Qingjing Liu
Supervisor: Professor Henry Sun
16 April 2012
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Pharmacometric Model Test on Theory of “Multi-components taking effect together” in Compound TCM (CDDP for example)
Background
Objective
Contents and Methods
Technical Route
Expected Results
Schedule
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Background ( cont)TCM : Multi-Components, Multi-Targets
TCM’s History of 2500 years formulae of 100,000
most formulae’s effective components are obscure need scientific test
From chemical research mode
single target, high affinity multi-components, multi-targets
In China, promoted in program 973* the theory hypothesis of
“multi-components, multi-targets”
*:973 program of foundation research on key problems of formulae
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Background ( cont)TCM : Multi-Components, Multi-Targets ?
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Background ( cont)
TCM : Multi-Components, Multi-Targets ?
Which component or components can take effect?
What are the different weight to each effective component?
Questions:
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Background ( cont)
use extracts of TCM
NO sufficient pharmaceutical evidence to support
Animal trials Human trials
Which Component or Components Take Effect?
Most experimental results come from animal expermients
focus on pharmacokinetic trail
※Dissection of mechanisms of Chinese medicinal formula Realgar-Indigonaturalis as an effective treatment for promyelocytic leukemia from the view of molecular biology and biochemistry
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Background ( cont)
What are the Different Weight to each Effective Component?
Set of weights for effectiveness of each component
•WANG ZM, threshold method
•LI M, cluster-metrix sum method
•TAO GL, stratification method
Disadvantage: subjective Pharmacometric model to calculate the weights of each effective component
Advantage: calculate from total effectiveness to each effectiveness= 》 objective
Compound Danshen Dropping Pills( CDDP)
Salvia
CDDP Panax Notoginseng
Borneol
PK data Data available PD data
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To find out which component or components have the biggest weight on drug effect.
To make sure if the multi-components of CDDP all take effect in real meaning
To provide a selection of quality control index for CDDP
To provide a pharmacological quantative way to find out the effective component or components of a compound TCM and the corresponsive weights
Contents Methods
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Multivariate Nonlinear Regression
Statistical correlation analysis on C and E
Compartment model simulation
Comparative analysis between different PKPD
models
Literature data
Clinical trial data
PK modelC~T
DoseCalculated date
C’
PD trialE
Correlation analysis of
R
Effective Components
PD model selection of each effective
component
PK model of each effective component
PKPD model for one effective component
Total PKPD Model
Repeat for every effective
componentsWeights of different
components
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Expected Results
Bring out an effective pharmacometric way of finding out the effective components of a compound TCM
Set up a PKPD model of CDDP
Calculate the weights of each effective component
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Schedule
2012.06
2012.07 – 2012.12
2013.01 – 2013.06
2013.07 – 2013.09
Research Proposal
Pharmacometrics learning&
SAS software study
Modeling and Simulation finish
Edit the first draft and finish the final edition
First draft finish
2013.10 – 2013.12
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Thank You