DDIapp —A Web‐Based Application for Static Drug–Drug Interaction Assessment

作者：Hirotaka Watase, Sylvie Klieber, Yorgos M. Psarellis, Nikhil Pillai, Panteleimon D. Mavroudis, Saroj Dhakal · 发表于：CPT Pharmacometrics & Systems Pharmacology · 年份：2026 · DOI：10.1002/psp4.70300 · 研究领域：Pharmacogenetics and Drug Metabolism、Drug-Induced Hepatotoxicity and Protection、Computational Drug Discovery Methods

ABSTRACT In this work we describe the development of a web‐based application for static drug–drug interaction (DDI) risk assessment in accordance with the International Council for Harmonization (ICH) M12 guidance. The app was built using the Shiny for Python framework and it employs a modular mathematical modeling structure that incorporates models for the assessment of enzyme inhibition, enzyme induction, and transporter inhibition at intestinal, hepatic, and renal levels. In addition, a “net effect” model estimates the combined impact of inhibition and induction on victim drug exposure, expressed as the area under the curve ratio ( AUCR ). Matrix‐specific approaches for estimating unbound fractions in microsomes and hepatocytes ( f u,mic and f u,hep ), as indicated in regulatory alignment, are implemented. The application provides a dynamic interface that supports flexible parameter input, real‐time evaluation across multiple DDI scenarios, and automated risk categorization using predefined thresholds based on the ICH M12 guidelines, with visual cues to aid risk interpretation. Additional features include integrated equation display for transparency and interpretation, export capabilities to PDF and Excel formats and a glossary with links to guidance documents and resources from major regulatory authorities (FDA, EMA, PMDA and NMPA). This DDIapp is validated against Certara's drug–drug interaction calculator under ICH M12 evaluation conditions. DDIapp offers a user‐friendl...