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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
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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 Technical Route Expected Results Schedule
Background(cont) TCM: Multi-Components, Multi-Targets • 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” • TCM’s History of 2500 years formulae of 100,000 most formulae’s effective components are obscure need scientific test *:973 program of foundation research on key problems of formulae
Background(cont) TCM: Multi-Components, Multi-Targets ?
Background(cont) TCM: Multi-Components, Multi-Targets ? Questions: Which component or components can take effect? What are the different weight to each effective component?
Background(cont) Which Component or Components Take Effect? NO sufficient pharmaceutical evidence to support • focus on pharmacokinetic trail Most experimental results come from animal expermients Animal trials Human trials • use extracts of TCM ※Dissection of mechanisms of Chinese medicinal formula Realgar-Indigo naturalis as an effective treatment for promyelocytic leukemia from the view of molecular biology and biochemistry
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
Background(cont) • Compound Danshen Dropping Pills( CDDP) Salvia • CDDP Panax Notoginseng Borneol PK data • Data available PD data
Objective • To provide a pharmacological quantative way to find out the effective component or components of a compound TCM and the corresponsive weights • To make sure if the multi-components of CDDP all take effect in real meaning • To find out which component or components have the biggest weight on drug effect. • To provide a selection of quality control index for CDDP
Contents & Methods • Contents • Methods Compartment model simulation Statistical correlation analysis on C and E Comparative analysis between different PKPD models Multivariate Nonlinear Regression
Technical Route Literature data Dose PK model C~T Calculated date C’ Clinical trial data PD trial E Correlation analysis of R PD model selection of each effective component Effective Components PKPD model for one effective component PK model of each effective component Repeat for every effective components Total PKPD Model Weights of different components
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
Schedule 2012.06 Research Proposal Pharmacometrics learning& SAS software study 2012.07 – 2012.12 2013.01 – 2013.06 Modeling and Simulation finish 2013.07 – 2013.09 First draft finish Edit the first draft and finish the final edition 2013.10 – 2013.12