Abstract

1. Quercetin (QCN) is commonly used in high doses as a dietary supplement for weight loss. Psychotic patients are at greater risk of developing obesity than the general population.

2. The present study was designed to understand the impact of QCN on the exposure of quetiapine (QTE), an anti-psychotic drug with narrow therapeutic index and brain penetrating capability. The content of QTE in rat plasma was analyzed through liquid chromatography–tandem mass spectrometry.

3. The results showed a significant (p < 0.05) increase in exposure of QTE (peroral dosed) in the animals pre-treated with QCN as compared to the control group. All the animals pre-treated with QCN, succumbed to death within 3–5 min of intravenous dosing of QTE (1 mg/kg). The studies in rat liver S9 fraction indicated that QCN could increase the metabolic stability of QTE by inhibiting the activity of CYP enzymes. The brain to plasma ratio of QTE increased upon QCN pre-treatment (2.6 vs 7.7), which could be attributed to P-glycoprotein inhibition at the blood–brain barrier by QCN.

4. The current set of studies indicated that serious herb–drug interaction between QCN and QTE might occur when they are co-administered. Caution is advised for concomitant use of QCN rich dietary supplements with QTE.

摘要

1. 槲皮素（QCN）通常以高剂量用作减肥食品。与一般人群相比，精神病患者患肥胖症的风险更大。

2. 本研究旨在了解QCN对喹硫平（QTE）暴露的影响，喹硫平是一种具有窄治疗指数和脑穿透能力的抗精神病药物。通过液相色谱-串联质谱法分析大鼠血浆中的QTE含量。

3. 结果显示 ，与对照组相比，经QCN预处理的动物的QTE（经口给药）的暴露量显着增加（p <0.05）。所有经QCN预处理的动物在静脉注射QTE（1 mg / kg）的3-5分钟内死亡。对大鼠肝脏S9组分的研究表明，QCN可以通过抑制CYP酶的活性来提高QTE的代谢稳定性。QCN预处理后，QTE的脑与血浆比例增加（2.6对7.7），这可能归因于QCN对血脑屏障中P-糖蛋白的抑制作用。

4. 当前的研究表明，当QCN和QTE并用时，它们之间可能会发生严重的草药相互作用。建议将QCN丰富的膳食补充剂与QTE并用。