Bioequivalence study of two metformin formulations.

A randomized single-dose cross-over study was conducted on 24 healthy male volunteers to compare the bioavailability of two metformin (CAS 657-24-9) tablet formulations, Emiphage (test) and a commercially available original preparation (reference). A dose of 850 mg was administered after an overnight fast with a washout period of seven days. Eighteen blood samples were collected over 32 h. Metformin concentrations in deproteinized serum were determined by a locally validated High Performance Liquid Chromatographic (HPLC) assay, and pharmacokinetic parameters were analyzed by the standard non-compartmental method. Mean +/- SD maximum concentration (C(max)), time to reach maximum concentration (T(max)), area under the curve (AUC(0 --> t) and AUC(0 --> infinity)), and elimination half-life (t(1/2)) were 1.73 +/- 0.54 and 1.86 +/- 0.67 microg/ml, 2.6 +/- 1.2 and 2.0 +/- 1.0 h, 10.72 +/- 3.93 and 10.82 +/- 3.72 microg x h/ml, 11.53 - 4.14 and 11.6 +/- 3.84 microg x h/ml, and 3.1 +/- 0.7 and 3.1 +/- 0.9 h for the test and reference formulation, respectively. The parametric 90% confidence intervals on the mean of the difference (test - reference) between log-transformed values of the two formulations were 82.92% to 98.78%, 85.95% to 101.47%, and 77.82% to 100.4% for AUC(0 --> t), AUC(0 --> infinity), and C(max), respectively. The results indicate that the two formulations can be considered equivalent in the extent of absorption under fasting conditions.