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