Bioequivalence evaluation of a combine formulation of pioglitazone/ metformin in healthy pakistani volunteers

Abstract

The purpose of this study was to evaluate bioequivalence of a combine formulation of pioglitazone/metformin 15/850 mg tablet with those of an established branded formulation. An open-label, single-dose, randomized, 2-way crossover study was conducted in fasted healthy Pakistani male volunteers. The concentrations of pioglitazone and metformin in plasma were analyzed by reverse phase High Performance Liquid Chromatography (HPLC). The plasma concentration-time curves were used to obtain pharmacokinetic parameters including AUC0-t, AUC0-∞, and Cmax. The formulations were considered bioequivalent if the 90% confidence intervals (CIs) for AUC, and Cmax fell within the interval of 80% to 125%, declared in bioequivalence guidelines. On analysis of variance, no period, formulation or sequence effects were observed for any pharmacokinetic property. The 90% confidence intervals of pioglitazone for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 93.34% to 103.12%, 86.15% to 106.03% and 85.62% to 107.41%, respectively. Similarly, the 90% CIs of metformin for the geometric mean ratios of Cmax, AUC0-t and AUC0-∞ were 87.64% to 100.85%, 86.68% to 116.15 and 94.14% to 122.71%, respectively, qualifying the predetermined criteria for bioequivalence based on the rate and extent of absorption. © 2011 Abbas M, et al.