Relevance of physicochemical properties and functional pharmacology data to predict the clinical safety profile of direct oral anticoagulants.

Ferro, Charles J and Solkhon, Fay and Jalal, Zahraa and Al-Hamid, Abdullah M and Jones, Alan M (2020) Relevance of physicochemical properties and functional pharmacology data to predict the clinical safety profile of direct oral anticoagulants. Pharmacology research & perspectives, 8 (3). e00603. ISSN 2052-1707. This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs

[img] Text (PDF file format)
prp2.603 - Published Version
Available under License Creative Commons Attribution No Derivatives 4.0.

Download (16kB)
Official URL: https://bpspubs.onlinelibrary.wiley.com/journal/20...

Abstract

Direct oral anticoagulants (DOACs) have rapidly become the drug class of choice for anticoagulation therapy in secondary care. It is known that gastrointestinal hemorrhage are potential side effects of the DOAC drug class. In this study we have investigated the relevance of molecular structure and on/off-target pharmacology as a predictor of adverse drug reactions (ADRs) for the DOAC drug class. Use of the Reaxys MedChem module allowed for data mining of all possible reported off-target effects of the DOAC class members. For the first time, the MHRA Yellow card database in combination with prescribing rates in the United Kingdom (data for n = 30 566 936 DOAC R (up to 2017) and ADR data n = 22 275 (up to 2018)) were used for our data comparison of DOACs. From the underlying reported data, we were able to rank the DOACs in terms of the likely adverse events we would expect to observe. We identified potential risks of ADRs based on the DOACs pharmacology including the expected GI hemorrhage, but also the unexpected risk of stroke, pulmonary embolism and kidney injury. Statistically significant (P < .001) differences were found between all DOACs and their total number of ADRs. Although the risks are small, strong statistical correlation between observed pharmacology and national ADR data is observed in three out of the five areas of concern.

Item Type: Article
Additional Information: This article is available to all UHB staff and students via ASK Discovery tool http://tinyurl.com/z795c8c by using their UHB Athens login IDs
Subjects: QV Pharmacology
W Public health. Health statistics. Occupational health. Health education
WH Haemic and lymphatic systems. Haematology
Divisions: Planned IP Care > Oncology and Clinical Haematology
Related URLs:
Depositing User: Jamie Edgar
Date Deposited: 18 Jun 2020 12:55
Last Modified: 18 Jun 2020 12:55
URI: http://www.repository.uhblibrary.co.uk/id/eprint/3180

Actions (login required)

View Item View Item