Salbutamol and Holoprosencephaly: A Novel Signal From Real-World Evidence
Author(s)
Glory Jenifer, MPH1, Eswaran Maheswari, PhD2.
1Student, M S Ramaiah University of Applied Sciences, Bangalore, India, 2Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bangalore, India.
1Student, M S Ramaiah University of Applied Sciences, Bangalore, India, 2Pharmacy Practice, M S Ramaiah University of Applied Sciences, Bangalore, India.
OBJECTIVES: Salbutamol, a β2-adrenergic receptor agonist, is widely used to treat bronchospasm in asthma and chronic obstructive pulmonary disease (COPD).This study aimed to investigate the novel adverse signals associated with salbutamol and perform molecular docking
METHODS: Pharmacovigilance signal detection was conducted using FDA Adverse Event Reporting System (FAERs) and OpenVigil database. The data was retrieved from FAERS using the terminologies such as salbutamol and albuterol as the preferred term (PT). Disproportionality analyses of PRR>2, ROR>2, chi-square >4 and drug events>2 confirms it as positive signal. Salbutamol targets were obtained from Swiss Target Prediction. Genes for the identified signal was retrieved from Gene Cards and OMIM. The common targets were identified and analysed for protein-protein interactions (PPIs) using the STRING database. Cytoscape and Cytohubba was used for network analysis to identify the hub genes. Molecular docking software was utilized to assess the binding affinities between salbutamol and hub genes.
RESULTS: FAERS data linked to salbutamol was 31,741 adverse events, including 2,076 deaths and 24,755 serious cases. Salbutamol revealed PRR of 6.17, ROR of 5.73 and chi square value of 35.0 with 5 adverse events. The Holoprosencephaly (HPE) is a rare congenital anomaly resulting from incomplete division of the prosencephalon during early embryogenesis, presenting with midline brain and facial malformations. Network pharmacology revealed 8 common targets from (100) salbutamol and (1,353) HPE-related genes. The top six hub genes with molecular docking revealed strong binding affinities of -4.979 (HDAC1), -5.736 (EHMT1), -5.031 (SIGMAR1), -6.167 (EHMT2), -7.168 (HDAC6), and -6.152 (EBP) supporting a potential mechanistic link.
CONCLUSIONS: This study suggests a novel association between salbutamol and holoprosencephaly, supported by pharmacovigilance, network pharmacology, and molecular docking. Further clinical and experimental research is essential to confirm this link and clarify underlying mechanisms.
METHODS: Pharmacovigilance signal detection was conducted using FDA Adverse Event Reporting System (FAERs) and OpenVigil database. The data was retrieved from FAERS using the terminologies such as salbutamol and albuterol as the preferred term (PT). Disproportionality analyses of PRR>2, ROR>2, chi-square >4 and drug events>2 confirms it as positive signal. Salbutamol targets were obtained from Swiss Target Prediction. Genes for the identified signal was retrieved from Gene Cards and OMIM. The common targets were identified and analysed for protein-protein interactions (PPIs) using the STRING database. Cytoscape and Cytohubba was used for network analysis to identify the hub genes. Molecular docking software was utilized to assess the binding affinities between salbutamol and hub genes.
RESULTS: FAERS data linked to salbutamol was 31,741 adverse events, including 2,076 deaths and 24,755 serious cases. Salbutamol revealed PRR of 6.17, ROR of 5.73 and chi square value of 35.0 with 5 adverse events. The Holoprosencephaly (HPE) is a rare congenital anomaly resulting from incomplete division of the prosencephalon during early embryogenesis, presenting with midline brain and facial malformations. Network pharmacology revealed 8 common targets from (100) salbutamol and (1,353) HPE-related genes. The top six hub genes with molecular docking revealed strong binding affinities of -4.979 (HDAC1), -5.736 (EHMT1), -5.031 (SIGMAR1), -6.167 (EHMT2), -7.168 (HDAC6), and -6.152 (EBP) supporting a potential mechanistic link.
CONCLUSIONS: This study suggests a novel association between salbutamol and holoprosencephaly, supported by pharmacovigilance, network pharmacology, and molecular docking. Further clinical and experimental research is essential to confirm this link and clarify underlying mechanisms.
Conference/Value in Health Info
2025-11, ISPOR Europe 2025, Glasgow, Scotland
Value in Health, Volume 28, Issue S2
Code
RWD170
Topic
Clinical Outcomes, Epidemiology & Public Health, Real World Data & Information Systems
Topic Subcategory
Distributed Data & Research Networks
Disease
Neurological Disorders