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)
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 a...
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MDPI AG
2022-03-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/7/2238 |
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| author | Amira Hussain Declan P. Naughton James Barker |
| author_facet | Amira Hussain Declan P. Naughton James Barker |
| author_sort | Amira Hussain |
| collection | DOAJ |
| description | 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 K<sub>i</sub> = 224.981 ± 1.854 µM and IC<sub>50</sub> = 230.552 ± 2.020 µM, although remdesivir showed a mixed inhibition pattern with a K<sub>i</sub> = 22.504 ± 0.008 µM and IC<sub>50</sub> = 45.007 ± 0.016 µM. Additionally, omeprazole uncompetitively inhibits dexamethasone metabolism by the CYP3A2 enzyme activity with a K<sub>i</sub> = 39.175 ± 0.230 µM and IC<sub>50</sub> = 78.351 ± 0.460 µM. These results suggest that the tested inhibitors would not exert a significant effect on the CYP3A2 isoenzyme responsible for the co-administered dexamethasone drug’s metabolism in vivo. |
| first_indexed | 2024-03-09T11:36:09Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T11:36:09Z |
| publishDate | 2022-03-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-aed59946d5ba4b38ae4fea6672d031b22023-11-30T23:41:28ZengMDPI AGMolecules1420-30492022-03-01277223810.3390/molecules27072238Potential 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)Amira Hussain0Declan P. Naughton1James Barker2School of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston-upon-Thames, London KT1 2EE, UKSchool of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston-upon-Thames, London KT1 2EE, UKSchool of Life Sciences, Pharmacy and Chemistry, Kingston University, Kingston-upon-Thames, London KT1 2EE, UKThe 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 K<sub>i</sub> = 224.981 ± 1.854 µM and IC<sub>50</sub> = 230.552 ± 2.020 µM, although remdesivir showed a mixed inhibition pattern with a K<sub>i</sub> = 22.504 ± 0.008 µM and IC<sub>50</sub> = 45.007 ± 0.016 µM. Additionally, omeprazole uncompetitively inhibits dexamethasone metabolism by the CYP3A2 enzyme activity with a K<sub>i</sub> = 39.175 ± 0.230 µM and IC<sub>50</sub> = 78.351 ± 0.460 µM. These results suggest that the tested inhibitors would not exert a significant effect on the CYP3A2 isoenzyme responsible for the co-administered dexamethasone drug’s metabolism in vivo.https://www.mdpi.com/1420-3049/27/7/2238cytochrome P450remdesiviromeprazoleibuprofenrat liver microsomesCYP3A activity |
| spellingShingle | Amira Hussain Declan P. Naughton James Barker 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 cytochrome P450 remdesivir omeprazole ibuprofen rat liver microsomes CYP3A activity |
| title | 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) |
| title_full | 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) |
| title_fullStr | 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) |
| title_full_unstemmed | 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) |
| title_short | 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) |
| title_sort | 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 |
| topic | cytochrome P450 remdesivir omeprazole ibuprofen rat liver microsomes CYP3A activity |
| url | https://www.mdpi.com/1420-3049/27/7/2238 |
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