Clinical translation of drug-drug interaction (DDI) studies is limited, and knowledge gaps across different types of DDI evidence make it difficult to consolidate and link them to clinical consequences. Consequently, we developed information retrieval (IR) models to retrieve DDI and drug-gene interaction (DGI) evidence from 25 million PubMed abstracts and distinguish DDI evidence into in vitro pharmacokinetic (PK), clinical PK, and clinical pharmacodynamic (PD) studies for US Food and Drug Administration (FDA) approved and withdrawn drugs. Additionally, information extraction models were developed to extract DDI-pairs and DGI-pairs from the IR-retrieved abstracts. An overlapping analysis identified 986 unique DDI-pairs between all 3 types of evidence. Another 2,157 and 13,012 DDI-pairs and 3,173 DGI-pairs were identified from known clinical PK/PD DDI, clinical PD DDI, and DGI evidence, respectively. By integrating DDI and DGI evidence, we discovered 119 and 18 new pharmacogenetic hypotheses associated with CYP3A and CYP2D6, respectively. Some of these DGI evidence can also aid us in understanding DDI mechanisms.

中文翻译：

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药物相互作用和药物遗传学之间的转化知识发现。

药物-药物相互作用（DDI）研究的临床翻译是有限的，并且不同类型DDI证据之间的知识鸿沟使得很难将其合并和关联到临床后果。因此，我们开发了信息检索（IR）模型，以从2500万PubMed摘要中检索DDI和药物基因相互作用（DGI）证据，并将DDI证据分为体外药代动力学（PK），临床PK和临床药效学（PD）研究，美国食品药品监督管理局（FDA）批准并撤回了药品。此外，开发了信息提取模型以从IR检索的摘要中提取DDI对和DGI对。重叠分析确定了所有3种证据之间的986个唯一DDI对。另外2,157和13,012个DDI对和3个，从已知的临床PK / PD DDI，临床PD DDI和DGI证据中分别鉴定出173个DGI对。通过整合DDI和DGI证据，我们分别发现了119和18个与CYP3A和CYP2D6相关的新的药物遗传学假设。这些DGI证据中的一些也可以帮助我们理解DDI机制。