Quercetin declines plasma exposure of metoprolol tartrate in the rat model

Challa, Siva Reddy; Challa, Venkatesh R; Ragam, Satheesh K

doi:10.4103/2231-4040.143038

Cited by 3 publications

(1 citation statement)

References 29 publications

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“…For example, Que has been demonstrated to increase the bioavailability of various drugs, including fexofenadine ( 43 ), rosiglitazone ( 44 ) and CsA ( 33 ) in humans; paclitaxel ( 45 ), valsartan ( 46 ), ranolazine ( 47 ), tamoxifen ( 48 ) and doxorubicin ( 49 ) in rats; and digoxin ( 50 ) in pigs. By contrast, Que decreased the bioavailability of talinolol ( 51 ) in humans, metoprolol ( 52 ) in rats, simvastatin ( 53 ) in pigs and CsA ( 32 , 34 – 36 ) in pigs and rats. Therefore, the HDIs of Que co-administration with other drugs, as well as the effect of Que on CYP3A and P-gp, remain to be fully elucidated.…”

Section: Discussionmentioning

confidence: 98%

Impact of quercetin-induced changes in drug-metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats

Liu

Luo

Yang

et al. 2016

Molecular Medicine Reports

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The aim of the present study was to evaluate whether quercetin (Que) modulates the mRNA and protein expression levels of drug-metabolizing enzymes (DMEs) and drug transporters (DTs) in the small intestine and liver, and thus modifies the pharmacokinetic profile of cyclosporine (CsA) in rats. This two-part study evaluated the pharmacokinetic profiles of CsA in the presence or absence of Que (experiment I) and the involvement of DMEs and DTs (experiment II). In experiment I, 24 rats received single-dose CsA (10 mg/kg) on day 1, single-dose Que (25, 50 and 100 mg/kg/day; eight rats in each group) on days 3–8, and concomitant CsA/Que on day 9. In experiment II, the mRNA and protein expression levels of cytochrome P (CYP)3A1, CYP3A2, UDP glucuronosyltransferase family 1 member A complex locus, organic anion-transporting polypeptide (OATP)2B1, OATP1B2, P-glycoprotein, breast cancer resistance protein, and multidrug resistance-associated protein 2 in the small intestine and liver of rats were analyzed following oral administration of Que at 25, 50 and 100 mg/kg in the presence or absence of CsA (10 mg/kg) for seven consecutive days. Co-administration of Que (25,50 and 100 mg/kg) decreased the maximum serum concentration of CsA by 46, 50 and 47% in a dose-independent manner. In addition, the area under the curve to the last measurable concentration and area under the curve to infinite time were decreased, by 21 and 16%, 30 and 33%, and 33 and 34% (P<0.01), respectively. However, the mRNA and protein expression levels of the above-mentioned DMEs and DTs were inhibited by Que in a dose-dependent manner (P<0.01) to a similar extent in the small intestine and liver. It was demonstrated that Que was able to reduce the bioavailability of CsA following multiple concomitant doses in rats. Overlapping modulation of intestinal and hepatic DMEs and DTs, as well as the DME-DT interplay are potential explanations for these observations.

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Section: Discussionmentioning

confidence: 98%

Impact of quercetin-induced changes in drug-metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats

Liu

Luo

Yang

et al. 2016

Molecular Medicine Reports

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Effects of Astragaloside IV on the Pharmacokinetics of Metoprolol in Rats and its Mechanism

Shi

Jiang

Zhao

et al. 2022

CDM

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Backgrond: Astragaloside IV (AST) and metoprolol are often used together to treat cardiovascular disease, while the potential of herb-drug interaction (HDI) between them is still unclear. Objective: This study investigates the effect of AST on the pharmacokinetics of metoprolol in rats and its mechanism to predict the potential of HDI Method: First, IC50 of AST on nine CYP450 enzymes in human liver microsomes (HLMs) was determined by the cocktail method. Then, we explored the effect of AST on the pharmacokinetics of metoprolol (metabolized by CYP2D6) in vivo. Twelve male SD rats were equally divided into two groups, with or without pretreatment of AST (3 mg/kg/day) for 7 days, and received metoprolol (27 mg/kg) by oral administration. Blood samples were determined using HPLC. Finally, its mechanism was explored. Results: AST exhibited a moderate inhibitory effect on CYP2D6 with IC50 of 32.28 µM. The pharmacokinetic parameters of metoprolol were significantly altered by AST with the increase of AUC0-∞ (538.81 ± 51.41 to 1088.34 ± 86.46 µg*min/mL, P<0.05) and Cmax (6.21 ± 0.56 to 8.34 ± 0.87 µg/ml, P<0.05). The investigation of the mechanism showed AST was an irreversible inhibitor of CYP2D6 with KI of 2.9 µM and Kinact of 0.018 min−1, Conclusion: It indicated that AST could increase the plasma exposure of metoprolol in rats. The mechanism might be that AST reduced the metabolism of metoprolol by inhibiting CYP2D6 activity. The potential of HDI might occur when they were applied in combination.

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Influence of Quercetin Pretreatment on Pharmacokinetics of Warfarin in Rats

Jahangir

Ahmạd

Ismail

et al. 2023

CDS

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Background: Warfarin (WAR) is a narrow therapeutic index anticoagulant and is principally metabolized by CYP3A4 and CYP2C9 enzymes. The inhibitors of the above enzymes may alter the systemic exposure of WAR. Quercetin (QUE), a bioflavonoid may modify the bioavailability of drugs used concurrently by inhibiting CYP3A4, CYP2C8, CYP2C9, CYP1A2 and P-glycoprotein (P-gp). Objective: The current study scrutinized the influence of QUE on WAR pharmacokinetics in rats. Method: QUE was orally administered to animals for 14 consecutive days followed by WAR as a single dose on 15th day in pre-treatment group. The co-administration group received a single dose of QUE and WAR, concomitantly. To control, only carboxymethylcellulose (CMC) 0.5% was administered as a vehicle. Result: In the pre-treated group, WAR’s Cmax was increased by 30.43%, AUC0-∞ by 62.94%, and t1/2 by 10.54%, while Cl decreased by 41.35%, relative to control. In co-administered animals, WAR’s Cmax increased by 10.98%, AUC0-∞ by 20.20%, and t1/2 by 8.87%, while Cl was declined by 16.40%. Conclusion: QUE alters the pharmacokinetics of WAR, warranting possibly WAR dose adjustment after confirmatory clinical investigations, specifically in patients with thrombotic disorders and a pre-treatment history of QUE or its product.

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Quercetin declines plasma exposure of metoprolol tartrate in the rat model

Cited by 3 publications

References 29 publications

Impact of quercetin-induced changes in drug-metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats

Impact of quercetin-induced changes in drug-metabolizing enzyme and transporter expression on the pharmacokinetics of cyclosporine in rats

Effects of Astragaloside IV on the Pharmacokinetics of Metoprolol in Rats and its Mechanism

Influence of Quercetin Pretreatment on Pharmacokinetics of Warfarin in Rats

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