生物学的同等性とバイオアベイラビリティのジャーナル

概要

Bioequivalence of Glucophage® (Metformin) Tablets from Europe and the United States Tested in Healthy Volunteers

Christian Friedrich, Tobias Brand, Arne Ring and Thomas Meinicke

Objectives: To investigate whether Glucophage® (metformin) tablets from Europe are bioequivalent to Glucophage tablets from the United States (US) despite in vitro dissolution differences. Bioequivalence would indicate that global Phase III data collected with either product is valid for the registration of fixed-dose combinations with metformin in both regions. Research design and methods: This study included two parts, both of which were conducted according to a randomised, open-label, single-dose, two-period crossover design. The subjects of Part I (N=28) received the 1000 mg Glucophage products, and the subjects of Part II (N=28) received the 500 mg Glucophage products. Results: At both dose levels (1000 mg and 500 mg), administration of single doses of Glucophage from Europe and the US resulted in comparable exposures, as determined by AUC0-inf and Cmax of metformin. The geometric mean ratios of AUC0-inf and Cmax were close to 100%, and the 90% confidence intervals of AUC0-inf and Cmax were contained within the bioequivalence acceptance limits of 80% to 125%. Incidence of adverse events was low and randomly distributed between treatment groups. Conclusions: Glucophage tablets from Europe and the US were shown to be bioequivalent at doses of 1000 mg and 500 mg. Glucophage tablets from both markets were well tolerated by healthy male and female subjects