Title:Effects of Dietary Flavonoids on the Metabolism of Vortioxetine and
its Potential Mechanism
Volume: 31
Issue: 23
关键词:
槲皮素，芹菜素，伏替西汀，代谢，大鼠，药代动力学。
摘要:
Introduction: Quercetin and apigenin are two common dietary flavonoids widely found in
foods and fruits. Quercetin and apigenin can act as the inhibitors of CYP450 enzymes, which may affect
the pharmacokinetics of clinical drugs. Vortioxetine (VOR), approved for marketing by the Food and
Drug Administration (FDA) in 2013, is a novel clinical drug for treating major depressive disorder
(MDD).
Objective: This study aimed to evaluate the effects of quercetin and apigenin on the metabolism of VOR
in in vivo and in vitro experiments.
Methods: Firstly, 18 Sprague-Dawley rats were randomly divided into three groups: control group
(VOR), group A (VOR + 30 mg/kg quercetin) and group B (VOR + 20 mg/kg apigenin). We collected the
blood samples at different time points before and after the final oral administration of 2 mg/kg VOR. Subsequently,
we further used rat liver microsomes (RLMs) to investigate the half-maximal inhibitory concentration
(IC50) of the metabolism of vortioxetine. Finally, we evaluated the inhibitory mechanism of two
dietary flavonoids on VOR metabolism in RLMs.
Results: In animal experiments, we found AUC (0-∞) (area under the curve from 0 to infinity) and CLz/F
(clearance) to be obviously changed. Compared to controls, AUC (0-∞) of VOR in group A and group B
was 2.22 and 3.54 times higher, respectively, while CLz/F of VOR in group A and group B was significantly
decreased down to nearly two-fifth and one-third. In in vitro studies, the IC50 value of quercetin and
apigenin in the metabolic rate of vortioxetine was 5.323 μM and 3.319 μM, respectively. Ki value of
quercetin and apigenin was found to be 0.040 and 3.286, respectively, and the αKi value of quercetin and
apigenin was 0.170 and 2.876 μM, respectively.
Conclusion: Quercetin and apigenin exhibited inhibitory effects on the metabolism of vortioxetine in vivo
and in vitro. Moreover, quercetin and apigenin had a mixed mechanism on the metabolism of VOR in
RLMs. Thus, we should pay more attention to the combination between these dietary flavonoids and VOR
in the future clinical use.
