Pharmacokinetics Interaction between Imatinib and Genistein in Rats

Wang, Zhe; Wang, Lili; Xia, Meng-Ming; Wei, Sun; Huang, Chengke; Cui, Xiaoli; Hu, Guoxin; Lian, Qingquan; Zeng-shou, Wang

doi:10.1155/2015/368976

Cited by 5 publications

(4 citation statements)

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“…Genistein intake was correlated with an enhanced multidrug chemoresistance in hepatocellular carcinoma (Rigalli et al, 2015). Pharmacokinetic interactions of genistein and imatinib were evaluated in rats and genistein seems to decrease imatinib plasma levels probably through effects on cytochrome CYP3A4; however the clinical significance of the pharmacokinetic interaction between imatinib and genistein still needs to be confirmed through further studies (Wang et al, 2015). Therefore, considering the increasing interest and consumption of PhyEs, further studies about PhyEs-drugs interactions are urgently needed, since it is now proved that PhyEs intake can alter the efficacy and the safety of several drugs.…”

Section: Natural Xenoestrogensmentioning

confidence: 99%

Risks and benefits related to alimentary exposure to xenoestrogens

Paterni

Granchi

Minutolo

2017

Critical Reviews in Food Science and Nutrition

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Xenoestrogens are widely diffused in the environment and in food, thus a large portions of human population is worldwide exposed to them. Among alimentary xenoestrogens, phytoestrogens (PhyEs) are increasingly being consumed because of their potential health benefits, although there are also important risks associated to their ingestion. Furthermore, other xenoestrogens that may be present in food are represented by other chemicals possessing estrogenic activities, that are commonly defined as endocrine disrupting chemicals (EDCs). EDCs pose a serious health concern since they may cause a wide range of health problems, starting from pre-birth till adult lifelong exposure. We herein provide an overview of the main classes of xenoestrogens, which are classified on the basis of their origin, their structures and their occurrence in the food chain. Furthermore, their either beneficial or toxic effects on human health are discussed in this review.

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Section: Natural Xenoestrogensmentioning

confidence: 99%

Risks and benefits related to alimentary exposure to xenoestrogens

Paterni

Granchi

Minutolo

2017

Critical Reviews in Food Science and Nutrition

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“…In the current study, the dose of imatinib was chosen according to previous studies [14,[46][47][48][49][50][51]. On the other hand, the GS extracts doses in human are highly variable, which reach 2000 mg/day [52].…”

Section: Discussionmentioning

confidence: 99%

The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats

Darweesh

El‐Elimat

Zayed

et al. 2020

BMC Pharmacol Toxicol

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Background Imatinib is mainly metabolized by CYP3A4 and to a lesser extent by other isoenzymes, with N-desmethyl imatinib being its major equipotent metabolite. Being a CYP3A4 substrate, imatinib co-administration with CYP3A4 modulators would change its pharmacokinetic profile. The cancer chemoprevention potential and anticancer efficacy of many herbal products such as grape seed (GS) and green tea (GT) extracts had led to an increase in their concomitant use with anticancer agents. GS and GT extracts were demonstrated to be potent inhibitors of CYP3A4. The aim of this study is to investigate the effect of standardized GS and/or GT extracts at two different doses on the pharmacokinetics of imatinib and its metabolite, N-desmethyl imatinib, in SD-rats. Methods Standardized GS and/or GT extracts were administered orally once daily for 21 days, at low (l) and high (h) doses, 50 and 100 mg/kg, respectively, before the administration of a single intragastric dose of imatinib. Plasma samples were collected and analyzed for imatinib and N-desmethyl imatinib concentrations using LC-MS/MS method, then their non-compartmental pharmacokinetic parameters were determined. Results h-GS dose significantly decreased imatinib’s Cmax and the $$ {\mathrm{AUC}}_0^{\infty } $$ AUC 0 ∞ by 61.1 and 72.2%, respectively. Similar effects on N-desmethyl imatinib’s exposure were observed as well, in addition to a significant increase in its clearance by 3.7-fold. l-GT caused a significant decrease in imatinib’s Cmax and $$ {\mathrm{AUC}}_0^{\infty } $$ AUC 0 ∞ by 53.6 and 63.5%, respectively, with more significant effects on N-desmethyl imatinib’s exposure, which exhibited a significant decrease by 79.2 and 81.1%, respectively. h-GT showed similar effects as those of l-GT on the kinetics of imatinib and its metabolite. However, when these extracts were co-administered at low doses, no significant effects were shown on the pharmacokinetics of imatinib and its metabolite. Nevertheless, increasing the dose caused a significant decrease in Cmax of N-desmethyl imatinib by 71.5%. Conclusions These results demonstrated that the pharmacokinetics of imatinib and N-desmethyl imatinib had been significantly affected by GS and/or GT extracts, which could be partially explained by the inhibition of CYP3A-mediated metabolism. However, the involvement of other kinetic pathways such as other isoenzymes, efflux and uptake transporters could be involved and should be characterized. Graphical abstract

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“…Blood was withdrawn from the retro orbital plexus after 2 h. In the case of 6-MP blood sample was collected 1 h after dosing owing to its short half-life. The dose and time point of collection was chosen based on literature evidence and reported half-life of these drugs in rats such that the drug concentration would fall within the linearity range of our HPLC assays (Pestieau et al 2000; Wang et al 2015; Hoshino-Yoshino et al 2011; Harrison et al 1989; Tterlikkis et al 1977; Roffey et al 2003). Blood sample from each animal was collected in three tubes containing different anticoagulants i.e.…”

Section: Methodsmentioning

confidence: 99%

Effect of various anticoagulants on the bioanalysis of drugs in rat blood: implication for pharmacokinetic studies of anticancer drugs

Kulkarni¹,

Karanam

Gurjar

et al. 2016

SpringerPlus

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BackgroundPharmacokinetic studies are vital in development and optimization of drugs. While blood samples can be collected either in EDTA, heparin or citrate containing tubes for the estimation of drug levels in plasma, EDTA tubes are more commonly used. The purpose of this study was to evaluate the effects of anticoagulants on bioanalysis of drugs. Six drugs used extensively in cancer therapy were selected. Albino wistar rats (N = 6 per drug) were dosed with one of the following drugs intraperitoneally—pemetrexed (50 mg/kg), imatinib (50 mg/kg), erlotinib (25 mg/kg), meropenem (60 mg/kg), 6-mercaptopurine (20 mg/kg) and voriconazole (6 mg/kg). Blood samples were collected 2 h after dosing (1 h in 6-mercaptopurine group due to short half-life) by terminal bleeding from the retro-orbital plexus. Blood was collected in each of Disodium ETDA, heparin, trisodium citrate (TSC) and no anticoagulant (plain) tubes. Drug levels in these samples were determined by validated HPLC assays. ANOVA with Tukey’s post hoc test was performed to identify statistically significant differences in drug concentrations in anticoagulant tubes. p < 0.05 was considered statistically significant.ResultsSignificant differences in concentration between anticoagulant tubes was observed in case of erlotinib (p = 0.013) and meropenem (p = 0.00), while borderline statistical significance for pemetrexed (p = 0.076). TSC tubes overestimated erlotinib levels, heparin tubes underestimated meropenem concentrations and EDTA tubes overestimated pemetrexed concentrations.ConclusionsCareful selection of anti-coagulant is necessary for accurate characterization of pharmacokinetics of drugs. Routine use of EDTA tubes may lead to erroneous interpretation of pharmacokinetic data.Electronic supplementary materialThe online version of this article (doi:10.1186/s40064-016-3770-4) contains supplementary material, which is available to authorized users.

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Pharmacokinetics Interaction between Imatinib and Genistein in Rats

Cited by 5 publications

References 36 publications

Risks and benefits related to alimentary exposure to xenoestrogens

Risks and benefits related to alimentary exposure to xenoestrogens

The effect of grape seed and green tea extracts on the pharmacokinetics of imatinib and its main metabolite, N-desmethyl imatinib, in rats

Effect of various anticoagulants on the bioanalysis of drugs in rat blood: implication for pharmacokinetic studies of anticancer drugs

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