# DDIAgents: Mechanism-Conditioned Context Flow for Drug-Drug Interaction Prediction

arXiv: https://arxiv.org/abs/2606.31085 · HTML: https://mlsanity.com/paper/2606.31085/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 13 of its 56 references that are in the map.
- First posted on arXiv 30 Jun 2026.

## Builds on (most cited first, 13 of 13)

- [GPT-4 Technical Report](https://mlsanity.com/paper/2303.08774/) (2023)
- [The Llama 3 Herd of Models](https://mlsanity.com/paper/2407.21783/) (2024)
- [Reflexion: Language Agents with Verbal Reinforcement Learning](https://mlsanity.com/paper/2303.11366/) (2023)
- [GLM: General Language Model Pretraining with Autoregressive Blank Infilling](https://mlsanity.com/paper/2103.10360/) (2021)
- [Large Language Models Can Be Easily Distracted by Irrelevant Context](https://mlsanity.com/paper/2302.00093/) (2023)
- [Generalizing from a Few Examples: A Survey on Few-Shot Learning](https://mlsanity.com/paper/1904.05046/) (2019)
- [MedAgents: Large Language Models as Collaborators for Zero-shot Medical Reasoning](https://mlsanity.com/paper/2311.10537/) (2023)
- [Modeling polypharmacy side effects with graph convolutional networks](https://mlsanity.com/paper/1802.00543/) (2018)
- [MDAgents: An Adaptive Collaboration of LLMs for Medical Decision-Making](https://mlsanity.com/paper/2404.15155/) (2024)
- [SumGNN: Multi-typed Drug Interaction Prediction via Efficient Knowledge Graph Summarization](https://mlsanity.com/paper/2010.01450/) (2020)
- [Emerging Drug Interaction Prediction Enabled by Flow-based Graph Neural Network with Biomedical Network](https://mlsanity.com/paper/2311.09261/) (2023)
- [Comprehensive evaluation of deep and graph learning on drug-drug interactions prediction](https://mlsanity.com/paper/2306.05257/) (2023)
- [K-Paths: Reasoning over Graph Paths for Drug Repurposing and Drug Interaction Prediction](https://mlsanity.com/paper/2502.13344/) (2025)

## Abstract (arXiv)

Drug-drug interaction (DDI) prediction is essential for medication safety, yet it requires reasoning over heterogeneous biomedical evidence whose relevance changes across interaction mechanisms. We propose DDIAgents, a mechanism-conditioned multi-agent framework that performs DDI prediction through dynamic knowledge orchestration. Given a drug pair, a planner agent instantiates specialized expert agents, routes mechanism-relevant knowledge sources to each agent, and aggregates their analyses through a conclusion agent. By adapting context flow to the inferred interaction mechanism, DDIAgents reduces irrelevant information, supports complementary expert reasoning, and produces interpretable agent-level rationales. Extensive experiments on realistic DDI prediction benchmarks show that DDIAgents consistently outperforms existing feature-based, graph-based, LLM-based, and agent-based baselines. Beyond prediction performance, DDIAgents demonstrates how multi-agent systems can organize heterogeneous scientific knowledge for adaptive and interpretable AI4Science reasoning.