Pharmacokinetic Interaction Between Eperisone and Ojeok-San in Healthy Subjects

Abstract

Ojeok-san is a traditional multiherbal formulation commonly prescribed for musculoskeletal symptoms in East Asian medicine. The concomitant use of herbal medicines and conventional pharmacotherapy is common in patients with musculoskeletal disorders; however, the pharmacokinetic (PK) interactions between eperisone and ojeok-san have not been evaluated. This was an open-label, randomized, single-dose, three-treatment, six-sequence, three-period crossover study designed to evaluate the PK interactions between eperisone and ojeok-san in 24 healthy male participants. In each period, participants received a single oral dose of 150 mg eperisone, 15.0 g ojeok-san, or 150 mg eperisone plus 15.0 g ojeok-san, with 7-day washout periods between treatments. Plasma concentrations of eperisone and ephedrine, a marker constituent of ojeok-san, were quantified using validated liquid chromatography–tandem mass spectrometry. Coadministration with ojeok-san reduced eperisone exposure, with geometric mean ratios (GMRs) for C_max and AUC_last of 0.34 (90% CI: 0.25-0.46) and 0.51 (90% CI: 0.41-0.64), respectively. In contrast, eperisone had little effect on ephedrine exposure, with GMRs for C_max and AUC_last of 1.04 (90% CI: 0.98-1.09) and 1.12 (90% CI: 1.05-1.20), respectively. No adverse events were reported. These findings demonstrated a PK interaction in which ojeok-san reduced systemic exposure to eperisone.