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<p>Escitalopram, a selective serotonin reuptake inhibitor (SSRI), treats depression and related anxiety symptoms by enhancing the physiological effects of serotonin (5-HT). This study explored the potential drug-drug interactions (DDIs) of combining escitalopram with flavonoid compounds (kaempferol and quercetin). The inhibitory effects of flavonoids on escitalopram metabolism were studied using human liver microsomes (HLM), rat liver microsomes (RLM) and Sprague–Dawley rats. The concentration of escitalopram and its metabolites were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Our findings revealed that the half-maximal inhibitory concentration (IC<sub>50</sub>) of kaempferol against escitalopram in HLM and RLM were 14.34 and 8.69&#xa0;μM, respectively, and both were mixed inhibitory mechanisms, consisting of competitive and non-competitive inhibition in HLM and non-competitive and un-competitive inhibition in RLM, respectively. Moreover, the IC<sub>50</sub> of quercetin against escitalopram in HLM and RLM were 11.25 and 8.14&#xa0;μM, respectively, and the inhibitory mechanisms were both mixed inhibitory mechanisms consisting of non-competitive and un-competitive inhibition. The in vivo results showed that quercetin significantly increased the AUC<sub>(0-t)</sub>, AUC<sub>(0-∞)</sub> and C<sub>max</sub> of escitalopram by 0.91-, 0.90- and 1.83-fold, respectively, while kaempferol and quercetin significantly reduced the CL<sub>z/F</sub> by 41.3% and 44.7%, respectively. In addition, kaempferol reduced the C<sub>max</sub> of N-desmethyl escitalopram by 62.1%. Therefore, the inhibitory effects of kaempferol and quercetin on the metabolism of escitalopram carries the risk of causing DDI and requires caution in combination.</p>

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Exploring the impacts of flavonoid compounds on escitalopram metabolism: a combined in vitro and in vivo study

  • 期刊论文

  • 发表日期：

    2026年1月7日

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  • Hailun Xia,
  • Jun Wu,
  • Haoxin Fu,
  • Peiqi Wang,
  • Ruibin Li,
  • Lu Cao,
  • Ya-nan Liu,
  • Lu Shi,
  • Ren-ai Xu

摘要

Escitalopram, a selective serotonin reuptake inhibitor (SSRI), treats depression and related anxiety symptoms by enhancing the physiological effects of serotonin (5-HT). This study explored the potential drug-drug interactions (DDIs) of combining escitalopram with flavonoid compounds (kaempferol and quercetin). The inhibitory effects of flavonoids on escitalopram metabolism were studied using human liver microsomes (HLM), rat liver microsomes (RLM) and Sprague–Dawley rats. The concentration of escitalopram and its metabolites were detected by ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Our findings revealed that the half-maximal inhibitory concentration (IC50) of kaempferol against escitalopram in HLM and RLM were 14.34 and 8.69 μM, respectively, and both were mixed inhibitory mechanisms, consisting of competitive and non-competitive inhibition in HLM and non-competitive and un-competitive inhibition in RLM, respectively. Moreover, the IC50 of quercetin against escitalopram in HLM and RLM were 11.25 and 8.14 μM, respectively, and the inhibitory mechanisms were both mixed inhibitory mechanisms consisting of non-competitive and un-competitive inhibition. The in vivo results showed that quercetin significantly increased the AUC(0-t), AUC(0-∞) and Cmax of escitalopram by 0.91-, 0.90- and 1.83-fold, respectively, while kaempferol and quercetin significantly reduced the CLz/F by 41.3% and 44.7%, respectively. In addition, kaempferol reduced the Cmax of N-desmethyl escitalopram by 62.1%. Therefore, the inhibitory effects of kaempferol and quercetin on the metabolism of escitalopram carries the risk of causing DDI and requires caution in combination.