1.Bioequivalence and pharmacokinetic comparison of two fixed dose combination of Metformin/Glibenclamide formulations in healthy subjects under fed condition
Chang Chee Tao ; Ang Ju Ying ; Wong Jia Woei ; Tan Siew Siew ; Chin Siaw Kuen ; Lim Ai Beoy ; Tan Weng Hong ; Yuen Kah Hay
The Medical Journal of Malaysia 2020;75(3):286-291
Aim: This study is conducted to compare the
pharmacokinetic profiles of two fixed dose combination of
metformin/glibenclamide tablets (500mg/5 mg per tablet).
Materials and Methods: 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.
Results: 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.
Conclusion: It can be concluded that the test preparation is
bioequivalent to the reference preparation.