Effect of Quercetin on the Plasma and Intracellular Concentrations of Saquinavir in Healthy Adults

DiCenzo, Robert; Frerichs, Valerie; Larppanichpoonphol, Panupong; Predko, Lisa; Chen, Amy; Reichman, Richard C.; Morris, Marilyn E.

doi:10.1592/phco.26.9.1255

Cited by 16 publications

(13 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…No effect (based on geometric mean rations of AUC, C (max), C (min) ) [175] Digoxin Drug against heart insufficiency 0.5 mg as single dose on day 6 1500 mg per day for 18 d (n =…”

Section: Discussionmentioning

confidence: 99%

“…In humans, mixed results regarding drug interactions were observed with single or repeated intakes of 300-1500 mg quercetin per day (Table 1). No significant changes of drug bioavailability were observed for nifedipine (antihypertensive drug), [173] rosiglitazone (antidiabetic drug), [174] saquinavir (anti-HIV drug), [175] digoxin, [74] warfarin (anticoagulant), [75] or cefprozil (antibiotic drug). [176] Reduced bioavailabilities (or only a trend without statistical significance) were reported for midazolam (sedative) [73,127] and talinolol (antihypertensive drug).…”

Section: Potential Drug Interactionsmentioning

confidence: 99%

“…[70,101,[161][162][163][164][165]178] However, other data are not in agreement with this hypothesis, revealing no change or a decrease in the bioavailability of drugs where primarily CYP3A4 and/or P-glycoprotein may be involved in the drug pharmacokinetics. [74,[167][168][169]173,175] Decreases in plasma levels of drugs during treatment with quercetin might also be explained by induced gene expressions of xenobiotic metabolizing enzymes or xenobiotic-transporting systems. Such processes would be expected to become more likely with increasing duration of quercetin exposure.…”

Section: Potential Drug Interactionsmentioning

confidence: 99%

See 2 more Smart Citations

Safety Aspects of the Use of Quercetin as a Dietary Supplement

Andres

Pevny

Ziegenhagen

et al. 2017

Molecular Nutrition Food Res

390

246

View full text Add to dashboard Cite

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.

show abstract

“…No effect (based on geometric mean rations of AUC, C (max), C (min) ) [175] Digoxin Drug against heart insufficiency 0.5 mg as single dose on day 6 1500 mg per day for 18 d (n =…”

Section: Discussionmentioning

confidence: 99%

Section: Potential Drug Interactionsmentioning

confidence: 99%

Section: Potential Drug Interactionsmentioning

confidence: 99%

See 1 more Smart Citation

Safety Aspects of the Use of Quercetin as a Dietary Supplement

Andres

Pevny

Ziegenhagen

et al. 2017

Molecular Nutrition Food Res

390

246

View full text Add to dashboard Cite

show abstract

“…That search identified 6 additional drugs, namely etoposide, folic acid, itraconazole, nizatidine, saquinavir, and theophylline, which exhibited AUC reductions of approximately 20%-40% with co-administration of apple juice, grapefruit juice, green tea, orange juice, or quercetin. [82][83][84][85][86][87][88] Available in vitro study results indicate that etoposide is a substrate of OATP2B1, 147 and saquinavir is a substrate of OATP1A2, with an uptake ratio of 2.14 and a K m value of 36.4 mM in transporterinjected oocytes. 34,148 Therefore, the slight exposure decrease (23%-24%) in etoposide and saquinavir when co-administered with grapefruit juice (100 mL single dose) and quercetin (500 mg 3 times daily for 8 days), respectively, could be caused by intestinal inhibition of OATPs.…”

Section: Additional Drugsmentioning

confidence: 99%

Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of Preclinical and Clinical Findings

Zhu

Tay-Sontheimer

et al. 2017

Journal of Pharmaceutical Sciences

104

View full text Add to dashboard Cite

In recent years, an increasing number of clinical drug-drug interactions (DDIs) have been attributed to inhibition of intestinal organic anion-transporting polypeptides (OATPs); however, only a few of these DDI results were reflected in drug labels. This review aims to provide a thorough analysis of intestinal OATP-mediated pharmacokinetic-based DDIs, using both in vitro and clinical investigations, highlighting the main mechanistic findings and discussing their clinical relevance. On the basis of pharmacogenetic and clinical DDI results, a total of 12 drugs were identified as possible clinical substrates of OATP2B1 and OATP1A2. Among them, 3 drugs, namely atenolol, celiprolol, and fexofenadine, have emerged as the most sensitive substrates to evaluate clinical OATP-mediated intestinal DDIs when interactions with P-glycoprotein by the test compound can be ruled out. With regard to perpetrators, 8 dietary or natural products and 1 investigational drug, ronacaleret (now terminated), showed clinical intestinal inhibition attributable to OATPs, producing ≥20% decreases in area under the plasma concentration-time curve of the co-administered drug. Common juices, such as apple juice, grapefruit juice, and orange juice, are considered potent inhibitors of intestinal OATP2B1 and OATP1A2 (decreasing exposure of the co-administered substrate by ∼85%) and may be adequate prototype inhibitors to investigate intestinal DDIs mediated by OATPs.

show abstract

“…The possible modification of plasma and cellular concentrations of SQV by quercetin, a bioflavonoid displaying inhibitory properties on CYP3A4 and P-gp, was investigated on 10 healthy adults who received SQV alone (1200 mg bid) for 11 days followed by the association SQV/quercetin (1200 mg bid/500 mg bid) during the next three days. [129] If no change was observed for SQV plasma concentration, its intracellular concentration surprisingly decreased by almost 50% when combined with quercetin.…”

Section: Drug-drug Interactions At the Intracellular Levelmentioning

confidence: 96%

Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action

Bazzoli

Jullien

Tiec

et al. 2010

Clinical Pharmacokinetics

145

101

View full text Add to dashboard Cite

In patients infected by HIV, the efficacy of highly active antiretroviral (ARV) therapy through the blockade of different steps of the retrovirus life cycle is now well established. As HIV is a retrovirus that replicates within the cells of the immune system, intracellular drug concentrations are important to determine ARV drug efficacy and toxicity. Indeed, nucleoside reverse transcriptase inhibitors (NRTIs), non-NRTIs (NNRTIs), newly available integrase inhibitors and protease inhibitors (PIs) act on intracellular targets. NRTIs are prodrugs that require intracellular anabolic phosphorylation to be converted into their active form of triphosphorylated NRTI metabolites, most of which have longer plasma half-lives than their parent compounds. The activity of intracellular kinases and the expression of uptake transporters, which may depend on cell functionality or their activation state, may greatly influence intracellular concentrations of triphosphorylated NRTI metabolites. In contrast, NNRTIs and PIs are not prodrugs, and they exert their activity by inhibiting enzyme targets directly. All PIs are substrates of cytochrome P450 3A, which explains why most of them display poor pharmacokinetic properties with intensive presystemic first-pass metabolism and short elimination half-lives. There is evidence that intracellular concentrations of PIs depend on P-glycoprotein and/or the activity of other efflux transporters, which is modulated by genetic polymorphism and coadministration of drugs with inhibiting or inducing properties. Adequate assay of the intracellular concentrations of ARVs is still a major technical challenge, together with the isolation and counting of peripheral blood mononuclear cells (PBMCs). Furthermore, intracellular drug could be bound to cell membranes or proteins; the amount of intracellular ARV available for ARV effectiveness is never measured, which is a limitation of all published studies. In this review, we summarize the findings of 31 studies that provided results of intracellular concentrations of ARVs in HIV-infected patients. Most studies also measured plasma concentrations, but few of them studied the relationship between plasma and intracellular concentrations. For NRTIs, most studies could not establish a significant relationship between plasma and triphosphate concentrations. Only eight published studies reported an analysis of the relationships between intracellular concentrations and the virological or immunological efficacy of ARVs in HIV patients. In prospective studies that were well designed and had a reasonable number of patients, virological efficacy was found to correlate significantly with intracellular concentrations of NRTIs but not with plasma concentrations. For PIs, the only prospectively designed trial of lopinavir found that virological efficacy was influenced by both trough plasma concentrations and intracellular concentrations. ARVs are known to cause important adverse effects through interference with cellular endogenous processes. The relationship between intr...

show abstract

Effect of Quercetin on the Plasma and Intracellular Concentrations of Saquinavir in Healthy Adults

Abstract: Quercetin coadministration did not influence plasma saquinavir concentrations. Because of substantial inter- and intrasubject variability, more study is necessary to determine if saquinavir intracellular concentrations are altered by coadministration of quercetin.

Cited by 16 publications

References 28 publications

Safety Aspects of the Use of Quercetin as a Dietary Supplement

Safety Aspects of the Use of Quercetin as a Dietary Supplement

Intestinal Drug Interactions Mediated by OATPs: A Systematic Review of Preclinical and Clinical Findings

Intracellular Pharmacokinetics of Antiretroviral Drugs in HIV-Infected Patients, and their Correlation with Drug Action

Contact Info

Product

Resources

About