{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:01:35Z","timestamp":1788778895127,"version":"build-2803163510"},"reference-count":58,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T00:00:00Z","timestamp":1655856000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000780","name":"European Union, co-financed by the European Social Fund","doi-asserted-by":"publisher","award":["EFOP-3.6.1.-16-2016-00004"],"award-info":[{"award-number":["EFOP-3.6.1.-16-2016-00004"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>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 \u03bcM 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.<\/jats:p>","DOI":"10.3390\/molecules27134000","type":"journal-article","created":{"date-parts":[[2022,6,22]],"date-time":"2022-06-22T23:11:19Z","timestamp":1655939479000},"page":"4000","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Intestinal and Biliary Metabolites of Ibuprofen in the Rat with Experimental Hyperglycemia"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2022-5077","authenticated-orcid":false,"given":"Hawsar Othman","family":"Mohammed","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"},{"name":"College of Veterinary Medicine, University of Sulaimani, Sulaymaniyah 46001, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Alm\u00e1si","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4244-0069","authenticated-orcid":false,"given":"Szil\u00e1rd","family":"Moln\u00e1r","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1057-9664","authenticated-orcid":false,"given":"P\u00e1l","family":"Perj\u00e9si","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Chemistry, Faculty of Pharmacy, University of P\u00e9cs, H-7624 P\u00e9cs, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1097\/FPC.0000000000000113","article-title":"PharmGKB summary: Ibuprofen pathways","volume":"25","author":"Mazaleuskaya","year":"2015","journal-title":"Pharmacogenet. 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