Imatinib and liver toxicity

Haq, Mohammad Inamul; Nixon, Joanna; Stanley, Adrian J.

doi:10.1136/bcr-2018-226740

Cited by 8 publications

(4 citation statements)

References 23 publications

(20 reference statements)

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“…Side effects remain one of the biggest drawbacks of the acute myeloid leukemia treatment because chemotherapy has a strong impact on patients’ quality of life and can sometimes discourage the patient from continuing treatment [ 46 ]. Similarly with chronic myeloid leukemia treatment, the prescribed tyrosine kinase inhibitor imatinib and others are associated with cases of liver toxicity [ 47 ], chronic fatigue [ 48 ], nausea, rash, superficial edema, muscle cramps, and myelosuppression [ 49 ].…”

Section: Resultsmentioning

confidence: 99%

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

et al. 2021

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Leukemia is a group of hematological neoplastic disorders linked to high mortality rates worldwide, but increasing resistance has led to the therapeutic failure of conventional chemotherapy. This study aimed to evaluate in vitro the antileukemic activity and potential mechanism of action of a polyphenolic extract obtained from the seeds of Coriandrum sativum L. (CSP). A methylthiazoletetrazolium assay was performed to assess the CSP cytotoxicity on chronic (K562) and acute (HL60) myeloid leukemia cell lines and on normal Vero cell line. CSP toxicity was also evaluated in vivo using the OECD 423 acute toxicity model on Swiss albino mice. The results demonstrated a remarkable antitumoral activity against K562 and HL60 cell lines (IC50 = 16.86 µM and 11.75 µM, respectively) although no cytotoxicity was observed for the Vero cells or mice. A silico study was performed on the following receptors that are highly implicated in the development of leukemia: ABL kinase, ABL1, BCL2, and FLT3. The molecular docking demonstrated a high affinity interaction between the principal CSP components and the receptors. Our findings demonstrated that CSP extract has remarkable antileukemic activity, which is mainly mediated by the flavonoids, catechins, and rutin, all of which showed the highest binding affinity for the targeted receptors. This study revealed a promising active compound alternative research-oriented biopharmacists to explore.

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Section: Resultsmentioning

confidence: 99%

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

et al. 2021

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“…We, therefore, cannot clarify whether the lower CL in patient is a result of the long-term treatment or whether there are further differences in the PK of imatinib between patients and healthy volunteers. Possibly, this might be a long-term side effect of imatinib due to its hepatotoxicity [ 46 ], but it could also be influenced by the chemotherapy, other co-medications, or disease progression. As described above, differences in plasma protein binding of imatinib between healthy subjects and patients may—in part—explain the observed differences in the two population studies here.…”

Section: Discussionmentioning

confidence: 99%

Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg

Chien

Würthwein

Zubiaur

et al. 2022

Cancer Chemother Pharmacol

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Purpose Imatinib is indicated for treatment of CML, GIST, etc. The population pharmacokinetics (popPK) of imatinib in patients under long-term treatment are reported in literature. Data obtained from bioequivalence trials for healthy subjects were used to evaluate the influence of demographic and pharmacogenetic factors on imatinib pharmacokinetics (PK) in a collective without concurrent drugs, organ dysfunction, inflammation etc. In addition, the differences in PK between the healthy subjects and a patient cohort was examined to identify possible disease effects. Methods 26 volunteers were administered orally with single dose of 400 mg imatinib. 16–19 plasma samples per volunteer were collected from 0.5 up to 72 h post-dose. The popPK was built and post hoc estimates were compared with previously published PK parameters evaluated by non-compartmental analysis in the same cohort. The predictivity of the model for data collected from 40 patients with gastrointestinal stromal tumors at steady state was evaluated. Results The popPK was best described by a two-compartment transit model with first-order elimination. No significant covariates were identified, probably due to the small cohort and the narrow range of demographic covariates; CYP3A5 phenotypes appeared to have some influence on the clearance of imatinib. Good agreement between non-compartment and popPK analyses was observed with the differences of the geometric means/ median of PK estimates below 10%. The model indicated lower clearance for patients compared to healthy volunteers (p value < 0.01). Conclusion The two-compartment transit model adequately describes the absorption and distribution of imatinib in healthy volunteers. For patients, a lower clearance of imatinib compared to healthy volunteer was estimated by the model. The model can be applied for dose individualization based on trough concentrations assuming no significant differences in absorption between patients and healthy volunteers.

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“…Safety and tolerability of chemotherapy have a significant influence on patients’ quality of life and may sometimes dissuade them from continuing the treatment [ 76 ]. Prescribed tyrosine kinase inhibitors, such as imatinib and others, have been linked to liver damage [ 77 ], chronic tiredness [ 78 ], nausea, rash, superficial edema, muscle cramps, and myelosuppression [ 79 ] similar to chronic myeloid leukemia therapy. The findings of both in vivo and in vitro experiments show that the PEMC has no toxicity, which enables to focus more attention on its antileukemic activity.…”

Section: Discussionmentioning

confidence: 99%

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

et al. 2022

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Natural products have offered a number of exciting approaches in cancer treatment over the years. In this study, we investigated the prophylactic and therapeutic effects of the polyphenol-enriched fraction extracted from Myrtus communis (PEMC) on acute and chronic leukemia. According to the UHPLC-MSn, the fraction is rich in flavonoids. Protective activity of the PEMC was assessed by evaluating the antioxidant, anti-inflammatory, wound healing, and hemolysis potential in a series of in vivo and in vitro assays, while the therapeutic approach consisted of the evaluation of cytotoxic activity of the PEMC against HL60 and K562 leukemia cell lines. Safety of the fraction was also evaluated on a non-cancerous Vero cell line and by an acute toxicity test performed in mice. The PEMC demonstrated a significant anti-inflammatory and healing potential. The activities found at the dose of 100 mg/kg were better than those observed using a reference drug. The PEMC demonstrated a significant antioxidant effect and a specific cytotoxicity towards HL60 (IC50 = 19.87 µM) and K562 (IC50 = 29.64 µM) cell lines being non-toxic to the Vero cell line. No hemolytic activity was observed in vitro and no toxicity effect was found in mice. Thus, the PEMC has a pharmacological potential as both preventive and therapeutic agent. However, further research is necessary to propose its mechanism of action.

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Imatinib and liver toxicity

Cited by 8 publications

References 23 publications

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

Antileukemic Activity and Molecular Docking Study of a Polyphenolic Extract from Coriander Seeds

Population pharmacokinetic modelling of imatinib in healthy subjects receiving a single dose of 400 mg

Antileukemic, Antioxidant, Anti-Inflammatory and Healing Activities Induced by a Polyphenol-Enriched Fraction Extracted from Leaves of Myrtus communis L.

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