The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia
Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyze...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/13/4000 |
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| author | Hawsar Othman Mohammed Attila Almási Szilárd Molnár Pál Perjési |
| author_facet | Hawsar Othman Mohammed Attila Almási Szilárd Molnár Pál Perjési |
| author_sort | Hawsar Othman Mohammed |
| collection | DOAJ |
| description | Hyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyzed oxidative metabolites. The present work aimed to investigate how experimental hyperglycemia affects the intestinal and biliary appearance of the oxidative and Phase II metabolites of ibuprofen in rats. In vivo studies were performed by luminal perfusion of 250 μM racemic ibuprofen solution in control and streptozotocin-treated (hyperglycemic) rats. Analysis of the collected intestinal perfusate and bile samples was performed by HPLC-UV and HPLC-MS. No oxidative metabolites could be detected in the perfusate samples. The biliary appearance of ibuprofen, 2-hydroxyibuprofen, ibuprofen glucuronide, hydroxylated ibuprofen glucuronide, and ibuprofen taurate was depressed in the hyperglycemic animals. However, no specific non-enzymatic (hydroxyl radical initiated) hydroxylation product could be detected. Instead, the depression of biliary excretion of ibuprofen and ibuprofen metabolites turned out to be the indicative marker of hyperglycemia. The observed changes impact the pharmacokinetics of drugs administered in hyperglycemic individuals. |
| first_indexed | 2024-03-09T12:46:01Z |
| format | Article |
| id | doaj.art-985de48e183047cc9c48bfddf8dceb0c |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T12:46:01Z |
| publishDate | 2022-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-985de48e183047cc9c48bfddf8dceb0c2023-11-30T22:12:54ZengMDPI AGMolecules1420-30492022-06-012713400010.3390/molecules27134000The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental HyperglycemiaHawsar Othman Mohammed0Attila Almási1Szilárd Molnár2Pál Perjési3Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, HungaryInstitute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, HungaryInstitute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, HungaryInstitute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Pécs, H-7624 Pécs, HungaryHyperglycemia is reported to be associated with oxidative stress. It can result in changes in the activities of drug-metabolizing enzymes and membrane-integrated transporters, which can modify the fate of drugs and other xenobiotics; furthermore, it can result in the formation of non-enzyme catalyzed oxidative metabolites. The present work aimed to investigate how experimental hyperglycemia affects the intestinal and biliary appearance of the oxidative and Phase II metabolites of ibuprofen in rats. In vivo studies were performed by luminal perfusion of 250 μM racemic ibuprofen solution in control and streptozotocin-treated (hyperglycemic) rats. Analysis of the collected intestinal perfusate and bile samples was performed by HPLC-UV and HPLC-MS. No oxidative metabolites could be detected in the perfusate samples. The biliary appearance of ibuprofen, 2-hydroxyibuprofen, ibuprofen glucuronide, hydroxylated ibuprofen glucuronide, and ibuprofen taurate was depressed in the hyperglycemic animals. However, no specific non-enzymatic (hydroxyl radical initiated) hydroxylation product could be detected. Instead, the depression of biliary excretion of ibuprofen and ibuprofen metabolites turned out to be the indicative marker of hyperglycemia. The observed changes impact the pharmacokinetics of drugs administered in hyperglycemic individuals.https://www.mdpi.com/1420-3049/27/13/4000ibuprofenstreptozotocinhyperglycemiaintestinal metabolismhepatic metabolismHPLC-MS |
| spellingShingle | Hawsar Othman Mohammed Attila Almási Szilárd Molnár Pál Perjési The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia Molecules ibuprofen streptozotocin hyperglycemia intestinal metabolism hepatic metabolism HPLC-MS |
| title | The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia |
| title_full | The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia |
| title_fullStr | The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia |
| title_full_unstemmed | The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia |
| title_short | The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia |
| title_sort | intestinal and biliary metabolites of ibuprofen in the rat with experimental hyperglycemia |
| topic | ibuprofen streptozotocin hyperglycemia intestinal metabolism hepatic metabolism HPLC-MS |
| url | https://www.mdpi.com/1420-3049/27/13/4000 |
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