Hannover Medical School, Institute of Pharmacology, Carl-Neuberg-Str. 1, 30625, Hannover, Germany.
Naunyn Schmiedebergs Arch Pharmacol. 2024 May;397(5):2995-3018. doi: 10.1007/s00210-023-02796-9. Epub 2023 Oct 23.
To gain a comprehensive overview of the landscape of clinical trials for the H-receptor antagonists (HR antagonists) cetirizine, levocetirizine, loratadine, desloratadine, and fexofenadine and their potential use cases in drug repurposing (the use of well-known drugs outside the scope of the original medical indication), we analyzed trials from clincialtrials.gov using novel custom-coded software, which itself is also a key emphasis of this paper. To automate data acquisition from clincialtrials.gov via its API, data processing, and storage, we created custom software by leveraging a variety of open-source tools. Data were stored in a relational database and annotated facilitating a specially adapted web application. Through the data analysis, we identified use cases for repurposing and reviewed backgrounds and results in the scientific literature. Even though we found very few trials with published results for repurpose indications, extended literature research revealed some prominent use cases: Cetirizine seems promising in mitigating infusion-associated reactions and is also more effective than placebo in the treatment of androgenetic alopecia. Loratadine may be beneficial in the prophylaxis of G-CSF-related bone pain. In COVID-19, HR antagonists may be helpful, but placebo-controlled scientific evidence is needed. For asthma, the effect of HR antagonists only seems to be secondary by alleviating allergy symptoms. Our novel method to find potential use cases for repurposing of HR antagonists allows for high automation, reduces human error, and was successful in revealing potential areas of interest. The software could be used for similar research questions and analyses in the future.
为了全面了解 H 受体拮抗剂(HR 拮抗剂)西替利嗪、左西替利嗪、氯雷他定、地氯雷他定和非索非那定的临床试验格局及其在药物重新定位(即超出原始医学适应证范围使用知名药物)中的潜在用途,我们使用新的定制软件分析了来自 clincialtrials.gov 的试验,该软件本身也是本文的一个重点。为了通过 clincialtrials.gov 的 API 自动获取数据、进行数据处理和存储,我们利用各种开源工具创建了定制软件。数据存储在关系数据库中,并进行了注释,以方便专门适配的 Web 应用程序使用。通过数据分析,我们确定了重新定位的用途,并在科学文献中回顾了背景和结果。尽管我们发现很少有针对重新定位适应证的试验具有已发表的结果,但扩展的文献研究揭示了一些突出的用途:西替利嗪在减轻输注相关反应方面似乎很有前景,在治疗雄激素性脱发方面也比安慰剂更有效。氯雷他定可能有助于预防 G-CSF 相关的骨痛。在 COVID-19 中,HR 拮抗剂可能有帮助,但需要有安慰剂对照的科学证据。对于哮喘,HR 拮抗剂的作用似乎只是通过缓解过敏症状而产生次要影响。我们发现 HR 拮抗剂重新定位潜在用途的新方法可以实现高度自动化、减少人为错误,并成功揭示了潜在的关注领域。该软件可用于未来类似的研究问题和分析。