A tool for integrating in vitro ADME data with chemical structure to predict human DDI.
DDI-Fusion Input Requirements |
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DDI-Fusion Data Delivery |
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DDI-Fusion integrates liver and gut PK data from chemPK™ with in vitro CYP interaction data in a KNIME workflow-based approach which executes the process illustrated in Figure 1.
KNIME can be downloaded easily and for free. Cyprotex can then provide the bespoke KNIME nodes (chemPK™ and DDI-Fusion) for the workflow.
Initially chemPK™ v2 predicts plasma and gut wall Cmax values. These parameters are used along with the in vitro inhibition and /or induction data as inputs to the DDI-Fusion node. This node then predicts the AUCRliver and AUCRgut for estimation of the AUCR.
Calculation of AUCR by DDI-Fusion | |||
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DDI-Fusion predicts AUCR of a co-administered victim drug (e.g., midazolam) in the presence of the perpetrator drug (test article).
If inhibitory effects dominate, AUCR>1 Additionally, DDI-Fusion predicts the contributions of DDI in (i) the gut (AUCRgut), and (ii) the liver (AUCRliver). AUCRtotal = AUCRgut wall x AUCRliver |
Regulatory Mechanistic Static Model | DDI-Fusion | |
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R2 | 0.63 | 0.70 |
RMSE | 3.67 | 2.53 |
GMFE | 1.58 | 1.36 |
We are looking for partners with whom we can further develop the DDI-Fusion model. If you would like to be involved then please get in touch.
Contact enquiries@cyprotex.com for a demonstration.