In Vitro Evaluation of Drug–Drug Interaction Between Gliclazide and Antacids at the Absorption Level

Slavica Lazarević; Srđan Kosijer; Maja Đanić; Dragana Zaklan; Bojan Stanimirov; Momir Mikov; Nebojša Pavlović

doi:10.3390/ph18050684

Pharmaceuticals (May 2025)

In Vitro Evaluation of Drug–Drug Interaction Between Gliclazide and Antacids at the Absorption Level

Slavica Lazarević,
Srđan Kosijer,
Maja Đanić,
Dragana Zaklan,
Bojan Stanimirov,
Momir Mikov,
Nebojša Pavlović

Affiliations

Slavica Lazarević: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
Srđan Kosijer: Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
Maja Đanić: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
Dragana Zaklan: Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
Bojan Stanimirov: Department of Biochemistry, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
Momir Mikov: Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia
Nebojša Pavlović: Department of Pharmacy, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia

DOI: https://doi.org/10.3390/ph18050684
Journal volume & issue: Vol. 18, no. 5
p. 684

Abstract

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Background: The antidiabetic drug gliclazide is often taken with antacids due to its gastrointestinal side effects. However, patients rarely report antacid use, making drug–drug 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.

Published in Pharmaceuticals

ISSN: 1424-8247 (Online)
Publisher: MDPI AG
Country of publisher: Switzerland
LCC subjects: Medicine: Pharmacy and materia medica
Website: http://www.mdpi.com/journal/pharmaceuticals/

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