Pharmacology and Toxicology Department From Meidicine Faculty, Universidad Autónoma de Nuevo León, Monterrey, Nuevo León, Mexico.
Research and Development Department, Laboratorios Silanes, S.A. de C.V., Mexico City, Mexico.
Adv Ther. 2019 Feb;36(2):407-415. doi: 10.1007/s12325-018-0853-3. Epub 2018 Dec 18.
Metformin tablets may be challenging to swallow not only for those patients with dysphagia but also for children and the elderly. A metformin solution was developed for easier administration and flexible dose adjustment mantained with the same bioavailability of tablets. The objective of this study was to assess the single-dose oral bioavailability of metformin hydrochloride administered as an oral solution (500 mg/5 mL) compared with metformin hydrochloride 500 mg tablets in fasting Mexican healthy volunteers.
A randomized, single dose, two-period, two-sequence, crossover study design with a 7-day washout interval was conducted. Subjects were randomly assigned to receive a single dose of 500 mg metformin hydrochloride, either as an oral solution (test drug) or as a tablet (reference drug), after 10 h of fasting. Plasma samples (16) were collected over a 16-h period after drug administration. Bioequivalence was declared when the ratio for the 90% confidence intervals (CI) of the difference in the means of the log-transformed area under the concentration-time curve from time 0 to the last observed concentration time (AUC), the area under the concentration-time curve extrapolated to infinite time (AUC), and the maximum plasma concentration (C) of the two products were within 0.80 and 1.25 interval. Plasma concentrations were analyzed using reverse phase chromatography by tandem mass spectrometry (LC-MS/MS). Safety and tolerability of metformin were also assessed in all subjects.
24 subjects were enrolled and completed the study (15 female and 9 male). Test and reference metformin hydrochloride were bioequivalent during the extent of exposure since AUC and C 90% CIs corresponded to 89.77-101.08% and 89.63-102.48%, respectively, both being within the pre-specified acceptance range criteria (80-125%). There were two adverse events (AE) with the reference formulation that were not related to the study drug.
Bioequivalence in healthy volunteers in fasting conditions of the two metformin hydrochloride formulations (oral solution and tablets) was established, being the difference in means of AUC, AUC and C within the acceptance range (80-125%). Oral solution formulation could offer the advantages of allowing adjusted doses and easier swallowing for every patient. Plain language summary is available for this article.
National Clinical Trials Registry (RNEC by its Spanish acronym), BD METF-Sil No. 86-15. Mexican Medicine Agency (COFEPRIS) Registry: 153300410B0368.
Laboratorios Silanes, S.A. de C.V.
二甲双胍片不仅对吞咽困难的患者，而且对儿童和老年人来说都难以吞咽。为了更方便给药和灵活调整剂量，同时保持与片剂相同的生物利用度，开发了一种二甲双胍溶液。本研究的目的是评估在空腹墨西哥健康志愿者中，以口服溶液（500mg/5mL）给予盐酸二甲双胍与盐酸二甲双胍 500mg 片剂相比的单剂量口服生物利用度。
这是一项随机、单剂量、两周期、两序列、交叉研究设计，洗脱期为 7 天。受试者禁食 10 小时后，随机接受 500mg 盐酸二甲双胍口服溶液（试验药物）或片剂（参比药物）单次给药。给药后 16 小时采集 16 个血浆样本。当两种产品的对数转换浓度-时间曲线下面积（AUC）从 0 到最后一个可观察浓度时间（AUC）、AUC 到无穷大时间（AUC）和最大血浆浓度（C）的差异的 90%置信区间（CI）比值在 0.80 至 1.25 区间内时，宣布生物等效性。使用液相色谱-串联质谱法（LC-MS/MS）对血浆浓度进行分析。所有受试者还评估了二甲双胍的安全性和耐受性。
共纳入 24 名受试者完成研究（15 名女性，9 名男性）。由于 AUC 和 C 90%CI 分别对应 89.77-101.08%和 89.63-102.48%，试验和参比盐酸二甲双胍在暴露程度上具有生物等效性，均在预定的可接受范围标准（80-125%）内。参比制剂有 2 例不良事件（AE）与研究药物无关。
在空腹条件下，两种盐酸二甲双胍制剂（口服溶液和片剂）在健康志愿者中具有生物等效性，AUC、AUC 和 C 的均值差异在可接受范围内（80-125%）。口服溶液制剂可为每位患者提供调整剂量和更易吞咽的优势。本文提供了通俗易懂的摘要。
国家临床试验注册处（RNEC），BD METF-Sil 编号 86-15。墨西哥药品管理局（COFEPRIS）注册：153300410B0368。
Silanes 实验室，S.A. de C.V.
