Hussain, Amira, Naughton, Declan P. and Barker, James (2022) Potential effects of ibuprofen, remdesivir and omeprazole on dexamethasone metabolism in control Sprague Dawley male rat liver microsomes (drugs often used together alongside COVID-19 treatment). Molecules, 27(7), p. 2238. ISSN (online) 1420-3049
Abstract
The role of individual cytochrome P450 (CYPs) responsible for the drug metabolism can be determined through their chemical inhibition. During the pandemic, dexamethasone and remdesivir with omeprazole were used for the treatment of COVID-19, while Ibuprofen was taken to treat the symptoms of fever and headache. This study aimed to examine the potency of ibuprofen remdesivir, and omeprazole as inhibitors of cytochrome P450s using rat liver microsomes in vitro. Dexamethasone a corticosteroid, sometimes used to reduce the body’s immune response in the treatment of COVID-19, was used as a probe substrate and the three inhibitors were added to the incubation system at different concentrations and analysed by a validated High Performance Liquid Chromatography (HPLC) method. The CYP3A2 isoenzyme is responsible for dexamethasone metabolism in vitro. The results showed that ibuprofen acts as a non-competitive inhibitor for CYP3A2 activity with Ki = 224.981 +/- 1.854 uM and IC50 = 230.552 +/- 2.020 uM, although remdesivir showed a mixed inhibition pattern with a Ki = 22.504 +/- 0.008 uM and IC50 = 45.007 +/- 0.016 uM. Additionally, omeprazole uncompetitively inhibits dexamethasone metabolism by the CYP3A2 enzyme activity with a Ki = 39.175 +/- 0.230 uM and IC50 = 78.351 +/- 0.460 uM. These results suggest that the tested inhibitors would not exert a significant effect on the CYP3A2.
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