Effect of Ginkgo tablets on the pharmacokinetics of metoprolol in rats: liquid chromatography-tandem mass spectrometry-based study.

Objectives: This study aimed to assess the interaction between metoprolol and Ginkgo tablets during their co-administration to provide a reference for clinical prescribing.

Methods: The co-administration of metoprolol (20 mg/kg) and Ginkgo tablets (2.4 mg/kg) was conducted in adult Sprague Dawley (SD) rats (n = 8). An optimized liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the analysis of plasma metoprolol to evaluate its pharmacokinetics. , the rat liver microsomes were employed to assess the effect of Ginkgo tablets on the metabolic stability of metoprolol and the activity of Cytochrome P450 2D6 (CYP2D6).

Results: The developed LC-MS/MS method was demonstrated of high sensitivity, accuracy, and precision. When co-administered with Ginkgo tablets, it increased the area under the curve (AUC, 59.01 ± 10.11 39.19 ± 10.21 μg/mL × min), the maximum plasma concentration (C, 461.72 ± 44.64 276.35 ± 118.09 ng/mL), and the half-life (t, 302.83 ± 91.52 262.34 ± 111.12 min) of metoprolol in rats and reduced the clearance rate (0.346 ± 0.057 0.539 ± 0.145 L/min/kg). , Ginkgo tablets improved the metabolic stability of metoprolol and suppressed the activity of CYP2D6 in a concentration-dependent manner with the IC value of 11.17 μM.

Conclusion: Co-administration of metoprolol with Ginkgo tablets resulted in increasing its systemic exposure through inhibiting CYP2D6 activity.