A tool for integrating in vitro ADME data with chemical structure to predict human DDI.
|DDI-Fusion Input Requirements|
|DDI-Fusion Data Delivery|
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|
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|
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 firstname.lastname@example.org for a demonstration.