Lazarević Slavica, Kosijer Srđan, Đanić Maja, Zaklan Dragana, Stanimirov Bojan, Mikov Momir, Pavlović Nebojša
Department of Pharmacology, Toxicology and Clinical Pharmacology, Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Faculty of Medicine, University of Novi Sad, 21000 Novi Sad, Serbia.
Pharmaceuticals (Basel). 2025 May 5;18(5):684. doi: 10.3390/ph18050684.
: 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. : 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. : 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. : 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.
抗糖尿病药物格列齐特因其胃肠道副作用常与抗酸剂一起服用。然而，患者很少报告使用抗酸剂的情况，这使得药物相互作用成为治疗失败的一个潜在原因。因此，本研究旨在研究各种抗酸剂对格列齐特渗透性的体外影响，并探索其潜在机制。
使用平行人工膜渗透性测定法（PAMPA）在四种介质（pH 1.2、pH 4.5、pH 6.8的缓冲液和水）中研究了单独的格列齐特以及在存在抗酸剂（碳酸氢钠、碳酸钙、氢氧化铝、水滑石和碳酸钙/碳酸镁）情况下的渗透性。计算了渗透系数，并评估了pH对格列齐特渗透性的影响。
在模拟空腹胃条件（pH 1.2）下，碳酸钙、水滑石以及碳酸钙/碳酸镁组合组的格列齐特渗透性显著高于对照组。在进食状态的胃条件（pH 4.5）下，只有水滑石没有显著改变格列齐特的渗透性。作为空腹状态肠液代表的pH 6.8条件下，碳酸氢钠、氢氧化铝和水滑石与对照组相比显著降低了格列齐特的渗透性。
抗酸剂在不同pH值下显著影响格列齐特的渗透性，可能会影响其生物利用度。格列齐特的渗透性主要受pH依赖性电离影响，尽管络合或盐形成也可能起作用。由于格列齐特和抗酸剂都与食物一起服用，且格列齐特主要在小肠吸收，因此钙基和镁基抗酸剂可被认为是最合适的选择。
