Effect of quercetin on P-glycoprotein transport ability in Chinese healthy subjects

Sy, Wang; Km, Duan; Y, Li; Ye, Mei; Sheng, Huang; H, Liu; X, Mei; Ouyang, Wen; Hh, Zhou; Zq, Liu

doi:10.1038/ejcn.2013.5

Cited by 37 publications

(35 citation statements)

References 33 publications

(32 reference statements)

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“…The effect of quercetin on P-gp seems to be dual in nature. On the one hand, the study by Wang et al demonstrated a 20% reduction in talinolol exposure when coadministered with quercetin, which suggests P-gp induction by quercetin [86]. Furthermore, quercetin decreased the exposure of cyclosporine by 43.3% in rats [103].…”

Section: Quercetinmentioning

confidence: 98%

Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug–Drug Interaction Studies

et al. 2020

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Understanding transporter-mediated drug-drug interactions (DDIs) for investigational agents is important during drug development to assess DDI liability, its clinical relevance, and to determine appropriate DDI management strategies. P-glycoprotein (P-gp) is an efflux transporter that influences the pharmacokinetics (PK) of various compounds. Assessing transporter induction in vitro is challenging and is not always predictive of in vivo effects, and hence there is a need to consider clinical DDI studies; however, there is no clear guidance on when clinical evaluation of transporter induction is required. Furthermore, there is no proposed list of index transporter inducers to be used in clinical studies. This review evaluated DDI studies with known P-gp inducers to better understand the mechanism and site of P-gp induction, as well as the magnitude of induction effect on the exposure of P-gp substrates. Our review indicates that P-gp and cytochrome P450 (CYP450) enzymes are coregulated via the pregnane xenobiotic receptor (PXR) and the constitutive androstane receptor (CAR). The magnitude of the decrease in substrate drug exposure by P-gp induction is generally less than that of CYP3A. Most P-gp inducers reduced total bioavailability with a minor impact on renal clearance, despite known expression of P-gp at the apical membrane of the kidney proximal tubules. Rifampin is the most potent P-gp inducer, resulting in an average reduction in substrate exposure ranging between 20 and 67%. For other inducers, the reduction in P-gp substrate exposure ranged from 12 to 42%. A lower reduction in exposure of the P-gp substrate was observed with a lower dose of the inducer and/or if the administration of the inducer and substrate was simultaneous, i.e. not staggered. These findings suggest that clinical evaluation of the impact of P-gp inducers on the PK of investigational agents that are substrates for P-gp might be warranted only for compounds with a relatively steep exposure-efficacy relationship.

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Section: Quercetinmentioning

confidence: 98%

Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug–Drug Interaction Studies

et al. 2020

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“…Such processes would be expected to become more likely with increasing duration of quercetin exposure. Quercetin may also have a different impact on certain genotypes, e.g., encoding for P‐glycoprotein (possibly via multi‐drug resistance gene induction) which could be also associated with an altered drug level . In addition, an inhibition of the organic anion‐transporting polypeptide 1B1 by quercetin has also been suggested .…”

Section: Safety Aspectsmentioning

confidence: 99%

Safety Aspects of the Use of Quercetin as a Dietary Supplement

Andres

Pevny

Ziegenhagen

et al. 2017

Molecular Nutrition Food Res

381

246

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The flavonoid quercetin is frequently found in low amounts as a secondary plant metabolite in fruits and vegetables. Isolated quercetin is also marketed as a dietary supplement, mostly as the free quercetin aglycone, and frequently in daily doses of up to 1000 mg d -1 exceeding usual dietary intake levels. The present review is dedicated to safety aspects of isolated quercetin used as single compound in dietary supplements. Among the numerous published human intervention studies, adverse effects following supplemental quercetin intake have been rarely reported and any such effects were mild in nature. Published adequate scientific data for safety assessment in regard to the long-term use (>12 weeks) of high supplemental quercetin doses (ࣙ1000 mg) are currently not available. Based on animal studies involving oral quercetin application some possible critical safety aspects could be identified such as the potential of quercetin to enhance nephrotoxic effects in the predamaged kidney or to promote tumor development especially in estrogen-dependent cancer. Furthermore, animal and human studies with single time or short-term supplemental quercetin application revealed interactions between quercetin and certain drugs leading to altered drug bioavailability. Based on these results, some potential risk groups are discussed in the present review.

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“…Even its extremely high-dietary intake can result in only nanomolar concentrations of total quercetin (the parent compound and its metabolites) in the circulation (Kelly, 2011); however, administration of dietary supplements with high-quercetin content (e.g., 500-1,000-mg aglycone in a single tablet/capsule) leads to micromolar plasma concentrations of total quercetin (Conquer, Maiani, Azzini, Raguzzini, & Holub, 1998;Heinz et al, 2010). In addition to its potential pharmacodynamic effects, quercetin can interact with serum albumin (causing displacement of drugs from albumin; Poór et al, 2013), cytochrome P450 (CYP) enzymes (Kimura, Ito, Ohnishi, & Hatano, 2010), and transport proteins (Wang et al, 2013). These effects may be responsible for pharmacokinetic interaction between quercetin and medications (Poór et al, 2017;Srinivas, 2015).…”

mentioning

confidence: 99%

Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high‐performance liquid chromatography

Vida

Fittler

Somogyi-Végh

et al. 2019

Phytotherapy Research

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Administration of the increasingly popular dietary supplements containing quercetin may interfere with drug therapy. We intended to evaluate the online availability and quercetin content of the high‐dose mono‐component quercetin products and to review the potential use of quercetin products and their interactions with drugs. We monitored the online access to quercetin‐containing dietary supplements, collected the relevant information from the websites, procured selected products from the vendors, and subjected them to substance analysis. The quercetin content was quantified by an HPLC‐UV method. Twenty‐five websites offered mono‐component quercetin products, and nine products were procured. The quercetin content of eight products differed only ±10% from the nominal dose, whereas one product contained almost 30% more quercetin. Misleading indications such as antitumor and cardiovascular effects were often found on the sellers' websites. Quercetin‐containing dietary supplements are available online with misleading indications. The recommended daily doses are often high (occasionally over 1,000 mg), which may induce clinically relevant interactions with medications. Because high‐quercetin content of dietary supplements was confirmed, health care professionals should be aware of the unregulated internet market of dietary supplements and should consider the interactions of these substances with drugs.

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Effect of quercetin on P-glycoprotein transport ability in Chinese healthy subjects

Abstract: Quercetin significantly induced the activity of P-gp and this induced effect was more obvious in MDR1 3435 TT individuals.

Cited by 37 publications

References 33 publications

Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug–Drug Interaction Studies

Effect of P-glycoprotein (P-gp) Inducers on Exposure of P-gp Substrates: Review of Clinical Drug–Drug Interaction Studies

Safety Aspects of the Use of Quercetin as a Dietary Supplement

Dietary quercetin supplements: Assessment of online product informations and quantitation of quercetin in the products by high‐performance liquid chromatography

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