Hospital Raja Permaisuri Bainun, Clinical Research Centre, Ipoh, Perak, Malaysia.
Attest Research Sdn Bhd, Kawasan Perindustrian Bayan Lepas, 11900 Penang, Malaysia.
Med J Malaysia. 2020 May;75(3):286-291.
This study is conducted to compare the pharmacokinetic profiles of two fixed dose combination of metformin/glibenclamide tablets (500mg/5 mg per tablet).
This is a single-center, single-dose, open-label, randomized, 2-treatment, 2-sequence and 2- period crossover study with a washout period of 7 days. All 28 adult male subjects were required to fast for at least 10 hours prior to drug administration and they were given access to water ad libitum during this period. Thirty minutes prior to dosing, all subjects were served with a standardized high-fat and high-calorie breakfast with a total calorie of 1000 kcal which was in accordance to the EMA Guideline on the Investigation of Bioequivalence. Subsequently, subjects were administered either the test or reference preparation with 240mL of plain water in the first trial period. During the second trial period, they received the alternate preparation. Plasma levels of glibenclamide and metformin were analysed separately using two different high performance liquid chromatography methods.
The 90% confidence interval (CI) for the ratio of the AUC0-t, AUC0-∞, and Cmax of the test preparation over those of the reference preparation were 0.9693-1.0739, 0.9598- 1.0561 and 0.9220 - 1.0642 respectively. Throughout the study period, no serious drug reaction was observed. However, a total of 26 adverse events (AE)/side effects were reported, including 24 that were definitely related to the study drugs, namely giddiness (n=17), while diarrheoa (n=3), headache (n=2) and excessive hunger (n=2) were less commonly reported by the subjects.
It can be concluded that the test preparation is bioequivalent to the reference preparation.
本研究旨在比较两种二甲双胍/格列本脲固定剂量复方片剂（每片 500mg/5mg）的药代动力学特征。
这是一项单中心、单剂量、开放标签、随机、2 种治疗、2 种序列和 2 期交叉研究，洗脱期为 7 天。所有 28 名成年男性受试者在给药前至少禁食 10 小时，并在此期间自由饮水。在给药前 30 分钟，所有受试者均给予符合 EMA 指导原则的标准化高脂肪、高热量早餐，总热量为 1000 卡路里。随后，受试者在第一试验期分别给予试验制剂或参比制剂，用 240mL 白开水送服。在第二试验期，他们服用另一种制剂。使用两种不同的高效液相色谱法分别分析格列本脲和二甲双胍的血浆水平。
试验制剂相对于参比制剂的 AUC0-t、AUC0-∞和 Cmax 的比值的 90%置信区间（CI）分别为 0.9693-1.0739、0.9598-1.0561 和 0.9220-1.0642。在整个研究期间，未观察到严重的药物不良反应。然而，共报告了 26 例不良事件（AE）/副作用，其中 24 例肯定与研究药物有关，即头晕（n=17），而腹泻（n=3）、头痛（n=2）和过度饥饿（n=2）较少被受试者报告。
可以得出结论，试验制剂与参比制剂生物等效。
