Abstrakt

Bioequivalence of a pioglitazone-glimepiride combination tablet versus coadministered single-dose pioglitazone and glimepiride in healthy Japanese subjects

Shinzo Hiroi, Kumi Matsuno, Masashi Hirayama, Kenji Kuriyama & Koji Kawakami

For patients with Type 2 diabetes mellitus (T2DM) who require combination antidiabetic drug therapy to achieve glycemic control, fixed-dose combinations have the potential to improve compliance. The objective of this study was to assess the bioequivalence of a fixed-dose combination of pioglitazone (PIO) 30 mg and glimepiride (GLIM) 3 mg relative to coadministered PIO 30 mg and GLIM 3 mg tablets. In an open-label, randomized, twoperiod, crossover study, 72 healthy Japanese men aged 20–35 years received a single dose of either the combination PIO/GLIM 30/3 mg tablet or coadministered PIO 30 mg and GLIM 3 mg tablets, followed by the alternative formulation after a washout period of ≥6 days. The primary pharmacokinetic end points were Cmax and AUC0–72h of unchanged PIO, and Cmax and AUC0–48h of unchanged GLIM. Bioequivalence was assessed by analysis of variance (ANOVA) using natural log-transformed Cmax and AUC values. The time courses of plasma concentrations of unchanged PIO and GLIM were similar for the fixed-dose combination and coadministered PIO 30 mg and GLIM 3 mg tablets. Application of ANOVA for natural log-transformed data indicated that 90% confidence intervals for the differences between formulations were entirely within the bioequivalence limit of ln(0.80) to ln(1.25). Both formulations were equally well tolerated. A fixed-dose combination PIO/GLIM 30/3 mg tablet was bioequivalent to coadministration of PIO 30 mg and GLIM 3 mg in healthy Japanese males, and was as well tolerated.