Bhutani Priyadeep, Rajanna Prabhakar K, Paul Atish T
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Rajasthan, India.
Pharmaceutical Candidate Optimization, Biocon Bristol Myers Squibb R&D Centre, Syngene International Limited, Bangalore, India.
Xenobiotica. 2020 Dec;50(12):1483-1489. doi: 10.1080/00498254.2020.1792002. Epub 2020 Jul 14.
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. 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. The results showed a significant ( < 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. 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.
槲皮素（QCN）通常以高剂量用作减肥的膳食补充剂。精神病患者比普通人群患肥胖症的风险更高。本研究旨在了解QCN对喹硫平（QTE）暴露的影响，QTE是一种治疗指数窄且具有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QTE的含量。结果显示，与对照组相比，用QCN预处理的动物中QTE（口服给药）的暴露量显著增加（<0.05）。所有用QCN预处理的动物在静脉注射QTE（1mg/kg）后3 - 5分钟内死亡。大鼠肝脏S9组分的研究表明，QCN可通过抑制CYP酶的活性来增加QTE的代谢稳定性。QCN预处理后，QTE的脑血比增加（2.6对7.7），这可能归因于QCN对血脑屏障处P-糖蛋白的抑制作用。目前的这组研究表明，QCN和QTE联合使用时可能会发生严重的药草 - 药物相互作用。建议谨慎将富含QCN的膳食补充剂与QTE同时使用。
