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

Abstract

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 Cmax (1757.7 to 1668.9 ng/mL) and AUClast (10407.4 to 9901.1 ng·h/mL), compared to those with metformin alone. Geometric mean ratios (90% Confidence Interval) of Cmax and AUClast 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 Cmax and AUClast. Considering the OGTT results, these changes in metformin concentration did not affect glucose concentration. In addition, there were no significant findings regarding safety profiles.