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DDIapp-A Web-Based Application for Static Drug-Drug Interaction Assessment
Hirotaka Watase1, Sylvie Klieber2, Yorgos M Psarellis3
1Quantitative Pharmacology Projects D-Japan, Translational Medicine Unit, R&D, Sanofi K.K., Tokyo, Japan.
CPT: Pharmacometrics & Systems Pharmacology
|July 26, 2026
Summary
A new web application, DDIapp, aids in assessing drug-drug interaction (DDI) risks based on International Council for Harmonization (ICH) M12 guidance. It models enzyme and transporter interactions to predict impacts on drug exposure, supporting research and regulatory decisions.
Area of Science:
- Pharmacology and Drug Metabolism
- Computational Chemistry
- Regulatory Science
Background:
- Drug-drug interactions (DDIs) pose significant risks to patient safety and therapeutic efficacy.
- Regulatory bodies like the ICH provide guidance (M12) for standardized DDI risk assessment.
- Existing tools may lack comprehensive modeling or user-friendly interfaces for DDI evaluation.
Purpose of the Study:
- To develop a web-based application (DDIapp) for static drug-drug interaction risk assessment.
- To implement a modular mathematical modeling structure aligned with ICH M12 guidance.
- To provide a user-friendly platform for evaluating DDI risks involving enzymes and transporters.
Main Methods:
- Developed a web application using the Shiny for Python framework.
- Incorporated modular mathematical models for enzyme inhibition/induction and transporter inhibition.
- Implemented matrix-specific approaches for estimating unbound fractions (fu,mic, fu,hep).
- Integrated a "net effect" model to estimate the area under the curve ratio (AUCR).
Main Results:
- The DDIapp provides a dynamic interface for flexible parameter input and real-time DDI scenario evaluation.
- Automated risk categorization with visual cues aids interpretation based on ICH M12 thresholds.
- Validated the application against Certara's drug-drug interaction calculator under ICH M12 conditions.
- The tool includes features like equation display, data export (PDF, Excel), and a regulatory glossary.
Conclusions:
- DDIapp offers a validated, user-friendly platform for static pharmacokinetic DDI risk assessment.
- The application supports scientific research and regulatory decision-making by evaluating perpetrator drug effects on victim drug exposure.
- Facilitates standardized DDI risk assessment in accordance with ICH M12 guidelines.
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