生物等效性和生物利用度杂志

抽象的

Bioequivalence and Pharmacokinetic Comparison of Two Metformin Immediate-release Formulations in Healthy Volunteers under Fed Conditions

Menon S, Kandari K, Mhatre M and Nair S

Background: Type-2 diabetes mellitus is a common metabolic disorder in Malaysia, where metformin is used as the first-line treatment. Since metformin absorption is altered when administered with food, the US FDA guidance on metformin hydrochloride recommended to conduct bioequivalence study in both fasting and fed conditions. In this study, we intended to establish bioequivalence between a locally manufactured metformin formulation with a reference formulation under fed condition.
Methods: The study was a single-dose, open label, randomised, two treatments, two periods, cross-over study in 24 healthy volunteers. The washout period was 7 days to allow adequate time for drug elimination from the body. Analysis of plasma metformin concentration was conducted with a validated reverse-phase HPLC with ultraviolet detection procedure. Non-compartmental modal was used to analyse the pharmacokinetic parameters. Tolerability of both formulations was assessed throughout the study.
Results: A total of 24 volunteers were recruited, only 21 had completed the study. Two volunteers dropped out of the study due to personal reason. The third volunteer experienced emesis within 4 hour post dose administration hence was not included into the analysis. There was no significant difference observed between the two formulations for the parameters assessed. The 95% confidence interval for the ratio of test over reference parameters were within the acceptance limits of 80.00% to 125.00%: Cmax 0.8864-1.0554, AUC0-t 0.8835-1.0184, AUC0-∞ 0.8933-1.0229. No serious adverse event was observed.
Conclusions: The test metformin 250 mg formulation was bioequivalent to the reference formulation.