Comparative pharmacokinetic profiles of selected irreversible tyrosine kinase inhibitors, neratinib and pelitinib, with apigenin in rat plasma by UPLC–MS/MS

Maher, Hadir M.; Alzoman, Nourah Z.; Shehata, Shereen M.; Abahussain, Ashwag O.

doi:10.1016/j.jpba.2017.01.039

Cited by 19 publications

(23 citation statements)

References 27 publications

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“…This effect cannot be solely attributed to apigenin, as chamomile tea is a very complex mixture of different compounds (flavonoids, coumarins, terpenoids, mucilage) . Animal studies have shown that the interactions between apigenin and certain anticancer agents, predominantly those metabolized by CYP3A4, have clinical relevance and might lead to severe adverse effects in cancer patients . Oral apigenin significantly increased the plasma levels of oral neratinib and pelitinib, irreversible tyrosine kinase inhibitors used in cancer treatment.…”

Section: Phase I Drug‐metabolizing Enzymesmentioning

confidence: 99%

“…For both anticancer agents, area under the plasma concentration‐time curve (AUC) extended by more than 50% (58% for neratinib, 53% for pelitinib). This increase in drug exposure might enhance both the incidence and intensity of the side effects of neratinib (diarrhea) and pelitinib (gastrointestinal and cutaneous effects) . Interesting results were obtained when investigating the effects of apigenin on the pharmacokinetics of another tyrosine kinase inhibitor, imatinib.…”

Section: Phase I Drug‐metabolizing Enzymesmentioning

confidence: 99%

“…22 Animal studies have shown that the interactions between apigenin and certain anticancer agents, predominantly those metabolized by CYP3A4, have clinical relevance and might lead to severe adverse effects in cancer patients. 23,24 Oral apigenin significantly increased the plasma levels of oral neratinib and pelitinib, irreversible tyrosine kinase inhibitors used in cancer treatment. For both anticancer agents, area under the plasma concentration-time curve (AUC) extended by more than 50% (58% for neratinib, 53% for pelitinib).…”

Section: Phase I Drug-metabolizing Enzymesmentioning

confidence: 99%

“…This increase in drug exposure might enhance both the incidence and intensity of the side effects of neratinib (diarrhea) and pelitinib (gastrointestinal and cutaneous effects). 24 Interesting results were obtained when investigating the effects of apigenin on the pharmacokinetics of another tyrosine kinase inhibitor, imatinib. Oral apigenin reduced the metabolism of oral imatinib (increase in AUC by 39.8%), whereas long-term administration (15 days) of apigenin stimulated it (decrease in AUC by 24.8%).…”

Section: Phase I Drug-metabolizing Enzymesmentioning

confidence: 99%

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Flavonoids as modulators of metabolic enzymes and drug transporters

Miron

Aprotosoaie

Trifan

et al. 2017

Annals of the New York Academy of Sciences

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Flavonoids, natural compounds found in plants and in plant-derived foods and beverages, have been extensively studied with regard to their capacity to modulate metabolic enzymes and drug transporters. In vitro, flavonoids predominantly inhibit the major phase I drug-metabolizing enzyme CYP450 3A4 and the enzymes responsible for the bioactivation of procarcinogens (CYP1 enzymes) and upregulate the enzymes involved in carcinogen detoxification (UDP-glucuronosyltransferases, glutathione S-transferases (GSTs)). Flavonoids have been reported to inhibit ATP-binding cassette (ABC) transporters (multidrug resistance (MDR)-associated proteins, breast cancer-resistance protein) that contribute to the development of MDR. P-glycoprotein, an ABC transporter that limits drug bioavailability and also induces MDR, was differently modulated by flavonoids. Flavonoids and their phase II metabolites (sulfates, glucuronides) inhibit organic anion transporters involved in the tubular uptake of nephrotoxic compounds. In vivo studies have partially confirmed in vitro findings, suggesting that the mechanisms underlying the modulatory effects of flavonoids are complex and difficult to predict in vivo. Data summarized in this review strongly support the view that flavonoids are promising candidates for the enhancement of oral drug bioavailability, chemoprevention, and reversal of MDR.

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Section: Phase I Drug‐metabolizing Enzymesmentioning

confidence: 99%

Section: Phase I Drug‐metabolizing Enzymesmentioning

confidence: 99%

Section: Phase I Drug-metabolizing Enzymesmentioning

confidence: 99%

Section: Phase I Drug-metabolizing Enzymesmentioning

confidence: 99%

See 2 more Smart Citations

Flavonoids as modulators of metabolic enzymes and drug transporters

Miron

Aprotosoaie

Trifan

et al. 2017

Annals of the New York Academy of Sciences

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“…Additionally, we reported a decrease in ERL and lapatinib bioavailability with green tea co‐administration, while significantly increased neratinib and pelitinib plasma levels were observed with co‐administration of apigenin. Such food–drug interactions are due to alterations in the activity of metabolizing enzymes and/or transporter proteins; therefore, patients taking TKIs should preferably avoid drinking green tea or taking apigenin during treatment with TKIs (Maher, Alzoman, Shehata, & Abahussain, ; Maher, Alzoman, Shehata, & Abahussain, ). Thus, particular attention should be paid to avoiding the concomitant administration of nutraceuticals with TKIs during the treatment regimen.…”

Section: Introductionmentioning

confidence: 99%

UPLC–MS/MS study of the effect of dandelion root extract on the plasma levels of the selected irreversible tyrosine kinase inhibitors dasatinib, imatinib and nilotinib in rats: Potential risk of pharmacokinetic interactions

Alzoman

Maher

Shehata

et al. 2019

Biomedical Chromatography

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Tyrosine kinase inhibitor treatments for chronic myeloid leukaemia based on nilotinib (NIL), dasatinib (DAS) and imatinib (IMA) have improved patient quality of life and have turned chronic myeloid leukemia from a fatal disease into a chronic disease.Dandelion is a rich source of phenolic compounds with strong biological properties, and the effects of using this plant in the treatment of different illnesses can be linked to the presence of various polyphenols found in the different parts of the plant. Thus, dandelion can potentially be used as a nutraceutical (dietary antioxidant) to prevent different disorders associated with oxidative stress, i.e. cardiovascular disorders, cancer and inflammatory processes. Mutual interference between a drug and a food constituent may result in altered pharmacokinetics of the drug and undesired or even dangerous clinical situations. In the present study, a bioanalytical ultra performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS) method was developed and validated for the quantification of DAS, IMA and NIL in rat plasma.Sample preparation was carried out using solid-phase extraction with C 18 cartridges with a good extraction recovery of ≥94.37% for the three drugs. The method was fully validated as per the US Food and Drug Administration guidelines.

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