Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats

Shin, Sang‐Chul; Choi, Jun‐Shik; Li, Xiuguo

doi:10.1016/j.ijpharm.2006.01.028

Cited by 155 publications

(103 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In rats, coadministration with dual P-gp and Cyp3a inhibitors resulted in an increased plasma AUC of tamoxifen, effects possibly mediated via Cyp3a inhibition (Shin et al, 2006;Piao et al, 2008). Upon administration of endoxifen itself in vivo we could directly observe the impact of P-gp on endoxifen oral availability.…”

Section: Discussionmentioning

confidence: 98%

P-Glycoprotein (ABCB1) Transports the Primary Active Tamoxifen Metabolites Endoxifen and 4-Hydroxytamoxifen and Restricts Their Brain Penetration

Iusuf

Teunissen²,

Wagenaar³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

P-glycoprotein (P-gp, ABCB1) is a highly efficient drug efflux pump expressed in brain, liver, and small intestine, but also in tumor cells, that affects pharmacokinetics and confers therapy resistance for many anticancer drugs. The aim of this study was to investigate the impact of P-gp on tamoxifen and its primary active metabolites, 4-hydroxytamoxifen, N-desmethyltamoxifen, and endoxifen. We used in vitro transport assays and Abcb1a/1b(Ϫ/Ϫ) mice to investigate the impact of P-gp on the oral availability and brain penetration of tamoxifen and its metabolites. Systemic exposure of tamoxifen and its metabolites after oral administration of tamoxifen (50 mg/kg) was not changed in the absence of P-gp. However, brain accumulation of tamoxifen, 4-hydroxytamoxifen, and N-desmethyltamoxifen were modestly, but significantly (1.5-to 2-fold), increased. Endoxifen, however, displayed a 9-fold higher brain penetration at 4 h after administration. Endoxifen was transported by P-gp in vitro. Upon direct oral administration of endoxifen (20 mg/kg), systemic exposure was slightly decreased in Abcb1a/1b(Ϫ/Ϫ) mice, but brain accumulation of endoxifen was dramatically increased (up to 23-fold at 4 h after administration). Shortly after high-dose intravenous administration (5 or 20 mg/kg), endoxifen brain accumulation was increased only 2-fold in Abcb1a/1b(Ϫ/Ϫ) mice compared with wild-type mice, suggesting a partial saturation of P-gp at the blood-brain barrier. Endoxifen, the clinically most relevant metabolite of tamoxifen, is a P-gp substrate in vitro and in vivo, where P-gp limits its brain penetration. P-gp might thus be relevant for tamoxifen/endoxifen resistance of P-gp-positive breast cancer and tumors positioned behind a functional blood-brain barrier.

show abstract

Section: Discussionmentioning

confidence: 98%

P-Glycoprotein (ABCB1) Transports the Primary Active Tamoxifen Metabolites Endoxifen and 4-Hydroxytamoxifen and Restricts Their Brain Penetration

Iusuf

Teunissen²,

Wagenaar³

et al. 2011

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…Latter, a 2006 study showed that the administration doses of 2.5, 7.5 and 15 mg/kg of quercetin to female Sprague-Dawley rats inhibits both MDR transporter-mediated efflux of tamoxifen and its first-pass metabolism [56]. Finally, in 2009 a study conducted in healthy humans showed that the treatment with 500 mg of quercetin during 7 days induced an increase of fexofenadine concentrations in blood plasma, probably through PGP inhibition mediated efflux [57].…”

Section: Quercetin Effect On Multidrug Re-sistancementioning

confidence: 99%

Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

Brito¹,

Ribeiro²,

Abrantes

et al. 2015

CMC

134

View full text Add to dashboard Cite

Abstract:Cancer is a problem of global importance, since the incidence is increasing worldwide and therapeutic options are generally limited. Thus, it becomes imperative to find new therapeutic targets as well as new molecules with therapeutic potential for tumors. Flavonoids are polyphenolic compounds that may be potential therapeutic agents. Several studies have shown that these compounds have a higher anticancer potential. Among the flavonoids in the human diet, quercetin is one of the most important. In the last decades, several anticancer properties of quercetin have been described, such as cell signaling, pro-apoptotic, anti-proliferative and anti-oxidant effects, growth suppression. In fact, it is now well known that quercetin has diverse biological effects, inhibiting multiple enzymes involved in cell proliferation, as well as, in signal transduction pathways. On the other hand, there are also studies reporting potential synergistic effects when combined quercetin with chemotherapeutic agents or radiotherapy. In fact, several studies which aim to explore the anticancer potential of these combined treatments have already been published, the majority with promising results. Actually it is well known that quercetin can act on the chemosensitization and radiosensitization but also as chemoprotective and radioprotective, protecting normal cells of the side effects that results from chemotherapy and radiotherapy, which obviously provides notable advantages in their use in anticancer treatment. Thus, all these data indicate that quercetin may have a key role in anticancer treatment. In this context, this review is focused on the relationship between flavonoids and cancer, with special emphasis on the role of quercetin.

show abstract

“…In the case of 5-FU, its membrane permeability increased as the amount of oil phase decreased at all S mix,2 ratios, while there were small differences in the permeability values for formulations C-H, which may have been due to their uniform content of oil phase and similar droplet size. The permeability of 5-FU from formulation E (S mix,2 1:1) was 3.05-fold greater compared to that of free 5 . The permeability of OXA, OXA/DCK complex, or 5-FU nanoemulsion across a Caco-2 cell monolayer displayed a tendency to increase as the weight ratio of S mix,2 to oil increased up to 3:1, and then significantly decreased at the ratio of 6:1.…”

Section: In Vitro Artificial Intestinal Membrane Permeabilitymentioning

confidence: 91%

Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

Pangeni¹,

Choi²,

Jeon³

et al. 2016

IJN

View full text Add to dashboard Cite

Enhanced bioavailability of tamoxifen after oral administration of tamoxifen with quercetin in rats

Cited by 155 publications

References 37 publications

P-Glycoprotein (ABCB1) Transports the Primary Active Tamoxifen Metabolites Endoxifen and 4-Hydroxytamoxifen and Restricts Their Brain Penetration

P-Glycoprotein (ABCB1) Transports the Primary Active Tamoxifen Metabolites Endoxifen and 4-Hydroxytamoxifen and Restricts Their Brain Penetration

Quercetin in Cancer Treatment, Alone or in Combination with Conventional Therapeutics?

Multiple nanoemulsion system for an oral combinational delivery of oxaliplatin and 5-fluorouracil: preparation and in vivo evaluation

Contact Info

Product

Resources

About