Impact of quercetin on pharmacokinetics of quetiapine: insights from in-vivo studies in wistar rats

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.

Keywords:

• Dietary supplement
• herb–drug interaction
• obesity
• pharmacokinetics
• quetiapine
• quercetin

Acknowledgements

Authors thank Dr. Saurabh Arora, Managing Director of Auriga Research Private Limited, India for helping with LC-MS/MS analysis. Authors also acknowledge Dr. Thanga Mariappan of Pharmaceutical Candidate Optimization, Biocon BMS R&D Centre (BBRC), Bristol Myers Squibb for review of the article. We acknowledge Invivo Biosciences, Bangalore, India and BITS, Pilani for necessary facility and support.

Disclosure statement

No potential conflict of interest was reported by the author(s).