Pharmaceutical Sciences Faculty, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
Chemistry Institute, Federal University of Alfenas, Alfenas, Minas Gerais, Brazil.
Int J Pharm. 2018 Dec 20;553(1-2):272-280. doi: 10.1016/j.ijpharm.2018.10.050. Epub 2018 Oct 23.
Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and according to in vitro data, GLIM form II is about 3.5 times more soluble and releases 2 times the drug amount than GLIM form I in the physiological pH range. Considering the literature in vitro data and that the diabetes treatment demands glycemic control, avoiding abrupt fluctuations in the blood glucose levels, this work aimed to study the impact of GLIM polymorphism in the in vivo performance of GLIM solid oral dosages. For this, hard gelatin capsules with GLIM form I or II were prepared and orally administered in rats. After that, pharmacokinetic studies were performed by sampling animal blood at different times, and biochemical parameters (pharmacodynamic), such as glucose and insulin, were also evaluated. Our results showed that the in vitro data corroborate with our in vivo assays. GLIM form II provided higher plasma concentration of drug than form I (at baseline up to approximately 200 min after oral administration) and, consequently, increased insulin release and reduced levels of glucose, showing good correlation between pharmacokinetic and pharmacodynamics assays. Thus, this study demonstrated that GLIM polymorphs in oral dosages might alter the drug efficacy, which may expose the patients to risks, such as hypoglycemia.
格列美脲（GLIM）被用作治疗 2 型糖尿病的口服抗高血糖药物。该药物有两种文献中描述的多晶型形式（GLIM 形式 I 和 GLIM 形式 II），根据体外数据，GLIM 形式 II 在生理 pH 范围内的溶解度约为 GLIM 形式 I 的 3.5 倍，释放的药物量是 GLIM 形式 I 的 2 倍。考虑到文献中的体外数据和糖尿病治疗对血糖控制的需求，避免血糖水平的急剧波动，这项工作旨在研究 GLIM 多态性对 GLIM 固体口服制剂体内性能的影响。为此，制备了含有 GLIM 形式 I 或 II 的硬明胶胶囊，并在大鼠中口服给药。之后，通过在不同时间采集动物血液进行药代动力学研究，并评估生化参数（药效学），如葡萄糖和胰岛素。我们的结果表明，体外数据与体内试验结果相符。GLIM 形式 II 比 GLIM 形式 I 提供更高的药物血浆浓度（在基线时高达口服给药后约 200 分钟），从而增加胰岛素释放并降低葡萄糖水平，显示药代动力学和药效学之间有良好的相关性。因此，这项研究表明，口服制剂中的 GLIM 多晶型可能会改变药物的疗效，这可能会使患者面临低血糖等风险。
