title: Opportunities for Web-based Drug Repositioning: Searching for Potential Antihypertensive Agents with Hypotension Adverse Events.
abstract: BACKGROUND
  Drug repositioning refers to the process of developing new indications for existing drugs. As a phenotypic indicator of drug response in humans, clinical side effects may provide straightforward signals and unique opportunities for drug repositioning.
  
  
  OBJECTIVE
  We aimed to identify drugs frequently associated with hypotension adverse reactions (ie, the opposite condition of hypertension), which could be potential candidates as antihypertensive agents.
  
  
  METHODS
  We systematically searched the electronic records of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) through the openFDA platform to assess the association between hypotension incidence and antihypertensive therapeutic effect regarding a list of 683 drugs.
  
  
  RESULTS
  Statistical analysis of FAERS data demonstrated that those drugs frequently co-occurring with hypotension events were more likely to have antihypertensive activity. Ranked by the statistical significance of frequent hypotension reporting, the well-known antihypertensive drugs were effectively distinguished from others (with an area under the receiver operating characteristic curve > 0.80 and a normalized discounted cumulative gain of 0.77). In addition, we found a series of antihypertensive agents (particularly drugs originally developed for treating nervous system diseases) among the drugs with top significant reporting, suggesting the good potential of Web-based and data-driven drug repositioning.
  
  
  CONCLUSIONS
  We found several candidate agents among the hypotension-related drugs on our list that may be redirected for lowering blood pressure. More important, we showed that a pharmacovigilance system could alternatively be used to identify antihypertensive agents and sustainably create opportunities for drug repositioning.
authors.affiliation: CoMed Technology & Consulting Co., Ltd., Hong Kong, China.
authors.forename: Kejian
authors.identifier: http://orcid.org/0000-0003-0617-0302
authors.initials: K
authors.lastname: Wang
authors.forename: Mei
authors.identifier: http://orcid.org/0000-0003-4145-0916
authors.initials: M
authors.lastname: Wan
authors.forename: Rui-Sheng
authors.identifier: http://orcid.org/0000-0002-8991-2684
authors.initials: RS
authors.lastname: Wang
authors.forename: Zuquan
authors.identifier: http://orcid.org/0000-0002-1089-8673
authors.initials: Z
authors.lastname: Weng
mesh_terms: D016907:Adverse Drug Reaction Reporting Systems; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D058492:Drug Repositioning; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D006973:Hypertension / Q000188:drug therapy; D007022:Hypotension / Q000139:chemically induced*; D020407:Internet; D060735:Pharmacovigilance; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D000959:Antihypertensive Agents
keywords: FAERS; FDA Adverse Event Reporting System; Web-based drug repositioning; antihypertensive drugs; big data; hypotension; openFDA