Pharmacokinetic and Pharmacodynamic Interaction of Metformin and Ojeok-san in Healthy Volunteers.

Purpose: This study aimed to evaluate the pharmacokinetics and pharmacodynamics of metformin and Ojeok-san (OJS) co-administration to healthy volunteers compared to those with metformin alone.

Methods: This was an open-label, one-sequence, crossover study, with two 2-day hospitalization schedules lasting up to 14 days. Metformin was administered once daily on days 1 and 2. OJS was administered alone three times a day on days 3-7 and co-administered with metformin once a day on days 8 and 9. Plasma concentrations of metformin were measured using a validated LC-MS/MS method. To evaluate pharmacodynamics, oral glucose tolerance tests (OGTTs) were performed on days 1, 2, 8 and 9.

Results: Fifteen participants were enrolled. The coadministration decreased C_max (1757.7 to 1668.9 ng/mL) and AUC_last (10407.4 to 9901.1 ng·h/mL), compared to those with metformin alone. Geometric mean ratios (90% Confidence Interval) of C_max and AUC_last between the co-administration with OJS and metformin alone were 92.15% (82.79-102.57) and 94.57% (85.6-104.48), respectively. Co-administration with OJS did not significantly change the mean glucose level compared to that with metformin alone.

Conclusion: Co-administration with OJS decreased the plasma concentrations of metformin compared to that with metformin alone. However, the degree of decrease was not significant based on the geometric mean of the C_max and AUC_last. Considering the OGTT results, these changes in metformin concentration did not affect glucose concentration. In addition, there were no significant findings regarding safety profiles.