Comparative Pharmacokinetic Study between Metformin Alone and Combined with Orlistat in Healthy Mexican Volunteers

Abstract

Traditional treatment of type 2 diabetes mellitus (T2DM) has focused on correcting hyperglycemia. However, T2DM is almost always accompanied by other conditions and risk factors that affect its morbidity and mortality. Obesity represents one of the main risk factors associated in the T2DM and a modest weight loss around 5% is linked with significant reduction in the blood glucose levels. The objective of this study was to compare the pharmacokinetic parameters between two formulations of metformin, alone or combined with orlistat, in healthy volunteers. A single-blinded, single dose, two-period, two-sequence, crossover, randomized and balanced study design with a 7-day washout period was performed in 26 Mexican volunteers. Plasma samples were collected over a 24-hour period after administration of 500 mg metformin alone or combined with 60 mg orlistat in each period. A validated high-performance liquid chromatography coupled with a ultraviolet detector was used to analyze metformin concentration in plasma. Bioequivalence between metformin alone and metformin combined with orlistat was determined when the ratio for the 90% confidence intervals (CI) of area under the curve (AUC 24h ) and maximum concentration (C max ) of the two formulations were within 80% and 125%. In the current study, the mean ± standard deviation (SD) of C max , AUC 24h and AUC ∞ of the formulation containing only metformin were 1.39 ± 0.44 μg/mL, 7.59 ± 3.17 μg h/mL and 8.48 ± 4.13 μg h/mL, respectively, while the mean ± SD of C max , AUC 24h and AUC ∞ of the formulation containing metformin and orlistat were 1.38 ± 0.48 μg/mL, 7.80 ± 2.83 μg h/mL and 9.13 ± 4.29 μg h/mL, respectively. The parametric 90% CI for C max and AUC 24h were 87.5-109.3 and 88.7-124.7, respectively. These results suggest that both formulations are bioequivalent and there is not pharmacokinetic interaction between metformin and orlistat.