{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,6]],"date-time":"2026-03-06T00:37:08Z","timestamp":1772757428883,"version":"3.50.1"},"reference-count":50,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T00:00:00Z","timestamp":1746403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Provincial Secretariat for Higher Education and Science","award":["003087686 2024 09418 003 000 000 001\/1"],"award-info":[{"award-number":["003087686 2024 09418 003 000 000 001\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Background: The antidiabetic drug gliclazide is often taken with antacids due to its gastrointestinal side effects. However, patients rarely report antacid use, making drug\u2013drug interactions a potential cause of therapy failure. Therefore, this study aimed to investigate the in vitro effects of various antacids on gliclazide permeability and to explore the underlying mechanisms. Methods: The permeability of gliclazide alone and in the presence of antacids (sodium bicarbonate, calcium carbonate, aluminum hydroxide, hydrotalcite and calcium carbonate\/magnesium carbonate) was investigated using the parallel artificial membrane permeability assay (PAMPA) in four media (buffers pH 1.2, pH 4.5, pH 6.8 and water). The permeability coefficients were calculated, and the effect of pH on gliclazide permeability was also evaluated. Results: At simulated fasting gastric conditions (pH 1.2), groups with calcium carbonate, hydrotalcite and the combination of calcium carbonate\/magnesium carbonate showed significantly higher permeability of gliclazide than the control group. At fed-state gastric conditions (pH 4.5), only hydrotalcite did not significantly change the permeability of gliclazide. Sodium bicarbonate, aluminum hydroxide and hydrotalcite significantly reduced the gliclazide permeability in comparison to the control group at pH 6.8 as a representative of fasted-state intestinal fluid. Conclusions: Antacids significantly impact the permeability of gliclazide at different pH values, potentially influencing its bioavailability. Gliclazide permeability is mainly influenced by pH-dependent ionization, though complex or salt formation may also play a role. Since both gliclazide and antacids are taken with food, and gliclazide is primarily absorbed in the small intestine, calcium- and magnesium-based antacids can be considered the most suitable choice.<\/jats:p>","DOI":"10.3390\/ph18050684","type":"journal-article","created":{"date-parts":[[2025,5,5]],"date-time":"2025-05-05T21:42:09Z","timestamp":1746481329000},"page":"684","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["In Vitro Evaluation of Drug\u2013Drug Interaction Between Gliclazide and Antacids at the Absorption Level"],"prefix":"10.3390","volume":"18","author":[{"given":"Slavica","family":"Lazarevi\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-8854-993X","authenticated-orcid":false,"given":"Sr\u0111an","family":"Kosijer","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7785-0666","authenticated-orcid":false,"given":"Maja","family":"\u0110ani\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7186-3212","authenticated-orcid":false,"given":"Dragana","family":"Zaklan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0708-3182","authenticated-orcid":false,"given":"Bojan","family":"Stanimirov","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2804-0624","authenticated-orcid":false,"given":"Momir","family":"Mikov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-5830","authenticated-orcid":false,"given":"Neboj\u0161a","family":"Pavlovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3085","DOI":"10.3748\/wjg.v21.i10.3085","article-title":"Association between diabetes mellitus and gastroesophageal reflux disease: A meta-analysis","volume":"21","author":"Sun","year":"2015","journal-title":"World J. 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