Evaluation of the bioequivalence of a fixed-dose combination tablet of pioglitazone–metformin versus commercial tablets in healthy Japanese male volunteers

Abstract

SUMMARY In chronic asymptomatic diseases such as Type 2 diabetes mellitus (T2DM) poor adherence to therapy is a common problem. Simplification of treatment regimens using fixed-dose combination formulations has the potential to improve patient compliance. In this randomized, crossover, single-dose study we evaluated the bioequivalence of a new fixed-dose combination of pioglitazone–metformin (30/500 mg) and commercial tablets (pioglitazone 30 mg plus metformin 2 × 250 mg) in 84 healthy Japanese male volunteers in a fasted state. The plasma concentration–time curves for unchanged pioglitazone and unchanged metformin were almost identical for the two formulations. The 90% confidence intervals for the ratios of maximum observed concentration (Cmax) and area under the plasma concentration–time curve from time 0 to 72 h (AUC0–72) for unchanged pioglitazone, and for Cmax and AUC0–48 of unchanged metformin, were within the 0.80–1.25 range, which meets the criterion for test-to-reference bioequivalence between th...