A single-dose, crossover study comparing the pharmacokinetics and pharmacodynamics of 2 formulations of metformin in healthy volunteers.

OBJECTIVE

To compare pharmacokinetics and pharmacodynamics of two formulations of metformin in healthy male volunteers under fasting conditions.

METHODS AND MATERIALS

This was a randomized, 3-treatment, 6-sequence, 3-period, crossover study in healthy Korean volunteers. Subjects received a placebo or a single oral dose of reference formulation (500-mg metformin hydrochloride) or a test formulation (571-mg metformin acetate). The pharmacodynamic profile was assessed according to the blood glucose level.

RESULTS

A total of 30 healthy male volunteers were included, although 2 of them withdrew consent before drug administration. For the test formulation, the mean (SD) pharmacokinetic parameters of Cmax and AUC(0-24) were 1,691 (476.7) μg/ ml and 11,081 (2,804.5) mg×h/ml, respectively. For the reference formulation, the mean (SD) pharmacokinetic parameters of C(max) and AUC(0-24) were 1,749 (494.4) mg/ml and 11,814 (3,344.2) mg×h/ml, respectively. The 90% CIs for the test:reference ratio were 86.6 - 103.5 for logarithm-transformed AUClast and 87.9 - 107.4 for logarithm-transformed C(max), respectively. In pharmacodynamic analysis, the average blood glucose levels were obtained in the first 4 hours and 5 - 8 hours after drug administration. The 90% CIs for the test:reference ratio of the average blood glucose level were 96.5 - 101.8 for the intervals up to 4 hours during continued fasting and 99.3 - 106.8 for 5 - 8 hours after drug administration, respectively.

CONCLUSION

The data suggests that the test and reference formulations meet the regulatory criteria for the pharmacokinetic equivalence in fasting healthy Korean male volunteers. The pharmacodynamic profile was similar between the test and reference formulations. Both metformin formulations appeared to be generally well-tolerated.