Abstract

This study investigated the impact of red ginseng extract (RGE) on the pharmacokinetics of nifedipine (NFD) and its primary metabolite, dehydronifedipine (DHNFD), in rats. A sensitive and robust analytical method was developed using liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of NFD and DHNFD in rat plasma. The method demonstrated high and reproducible extraction recovery rates, ranging from 84.50% to 91.06%, with no interference at the elu- tion peaks for NFD and DHNFD. Calibration curves for NFD (1–500 ng/mL) and DHNFD (0.3–50 ng/mL) exhibited linearity (r² > 0.984) and met standard criteria for inter- and intra-day accuracy, precision, and stability. Following an intravenous dose of NFD (0.2 mg/kg), no significant differences in the plasma concentrations of NFD and DHNFD were observed between the RGE-treated group (1.5 g/kg/day for 1 week) and the vehicle-treated group. However, after oral administration (1.0 mg/kg), the RGE-treated group exhibited increased plasma levels of NFD and decreased levels of DHNFD, indicating a distinct effect of RGE on oral, but not intravenous, NFD pharmacokinetics. While hepatic Cyp3a expression remained unchanged following RGE treatment, there was a reduction in Cyp3a levels in the enterocytes, suggesting that this downregulation in the gastrointestinal tract likely contributed to the altered pharmacokinetic profile observed with orally administered NFD. In conclusion, RGE administration affects the metabolism of NFD following its oral dosing, potentially through down regulation of intestinal Cyp3a protein levels, leading to reduced systemic DHNFD concentrations and increased NFD plasma exposure.