Analytical methodologies for determination of methotrexate and its metabolites in pharmaceutical, biological and environmental samples

Karami, Forough; Ranjbar, Sara; Ghasemi, Younes; Negahdaripour, Manica

doi:10.1016/j.jpha.2019.06.001

Cited by 61 publications

(37 citation statements)

References 141 publications

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“…However, MTX used in high doses in cancer therapy can also cause very serious, life-threatening side effects highly dependent on the treatment duration, age and condition of the patient. The minimal effective concentration and minimal toxic concentration of MTX is considerably small and the drug has a very narrow therapeutic range [127]. The risk of side effects is greater in patients regularly taking other medicines, especially NSAIDs like aspirin, ibuprofen or naproxen.…”

Section: Methotrexate-the Anti-tumour Agentmentioning

confidence: 99%

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Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Koźmiński

Halik

Chesori

et al. 2020

IJMS

204

120

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Methotrexate, a structural analogue of folic acid, is one of the most effective and extensively used drugs for treating many kinds of cancer or severe and resistant forms of autoimmune diseases. In this paper, we take an overview of the present state of knowledge with regards to complex mechanisms of methotrexate action and its applications as immunosuppressive drug or chemotherapeutic agent in oncological combination therapy. In addition, the issue of the potential benefits of methotrexate in the development of neurological disorders in Alzheimer’s disease or myasthenia gravis will be discussed.

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Section: Methotrexate-the Anti-tumour Agentmentioning

confidence: 99%

“…Nevertheless, HDMTX with LV rescue has been most commonly used in a therapeutic strategy in oncology for almost three decades [126,127].…”

Section: Methotrexate-the Anti-tumour Agentmentioning

confidence: 99%

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Koźmiński

Halik

Chesori

et al. 2020

IJMS

204

120

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“…Methotrexate (MTX) is an antimetabolite for folic acid ( Bluett et al, 2019 ). MTX is an essential component of therapy for acute lymphoblastic leukemia (ALL) and is active against many types of cancer; however, MTX use needs to be monitored for potential side effects, such as bone marrow suppression, alopecia, stomatitis and the development of hepatic fibrosis or cirrhosis ( De Abreu et al, 2015 ; Karami, et al, 2019 ). MTX doses of 500 mg/m 2 or higher given intravenously are defined as high-dose methotrexate (HD-MTX) ( Howard et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Relationship Between the Free and Total Methotrexate Plasma Concentration in Children and Application to Predict the Toxicity of HD-MTX

Dong

Guo

et al. 2021

Front. Pharmacol.

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High-dose methotrexate (HD-MTX) can be highly effective as well as extremely toxic. Many drug molecules can bind to plasma proteins to different extents in vivo, whereas only the free drug can reach the site of action to exert a pharmacological effect and cause toxicity. However, free MTX concentrations in plasma have not been reported. Traditional analyses of free drugs are both cumbersome and inaccurate. We collected 92 plasma samples from 52 children diagnosed with ALL or NHL or other lymphomas that were treated with HD-MTX. The hollow fiber centrifugal ultrafiltration (HFCF-UF) was used to prepare plasma samples for analysis of the free MTX concentration. Protein precipitation was employed to measure the total MTX concentration. The HFCF-UF is a simple method involving a step of ordinary centrifugation; the validation parameters for the methodological results were satisfactory and fell within the acceptance criteria. A linearity coefficient r2 of 0.910 was obtained for the correlation between the free and total MTX plasma concentrations in 92 plasma samples. However, the free and total MTX concentrations was only weakly correlated in 16 clinical plasma specimens with total MTX concentrations >2 μmol L−1 (r2 = 0.760). Both the free and total MTX concentrations at 42 h were negatively correlated with the creatinine clearance (CCr) level (P = 0.023, r = −0.236 for total MTX and P = 0.020, r = −0.241for free MTX, respectively). The free MTX concentration could not be accurately estimated from the total MTX concentration for patients with high MTX levels which are conditions under which toxic reactions are more likely to occur. High plasma MTX levels could become a predictor of the occurrence of MTX nephrotoxicity to draw people's attention. The proposed HFCF-UF method is a simple and accurate way to evaluate efficacy and toxicity in clinical therapeutic drug monitoring.

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“…Considering that MTX has a narrow therapeutic window, fluctuations in its blood concentration will limit its efficacy or cause serious side effects (16). In addition, the possibility of a drug interaction when WZC is combined with MTX necessitates the assessment of potential drug interactions between WZC and MTX.…”

Section: Introductionmentioning

confidence: 99%

Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp

Fu¹,

Wang²,

Guo³

et al. 2021

Ann Transl Med

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Background: Methotrexate (MTX) is an important anticancer agent and immunosuppressant with a narrow therapeutic window. Wuzhi capsule (WZC) is an extract of Schisandra which is widely used to treat liver diseases. Co-administration of MTX and WZC is common in the clinical setting, but research on the interaction between WZC and MTX is limited. This study aimed to investigate the effects of WZC on the pharmacokinetics of MTX in rats and to explore the role of membrane transport proteins OAT1/3 and P-gp in the interaction of these drugs.Methods: Plasma MTX concentration was detected by ultra-performance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS), and the messenger RNA (mRNA) and protein expression of OAT1/3 and P-gp was evaluated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blotting analyses, respectively. Results:The study results revealed that co-administration of WZC decreased the CL z/F and V z/F of MTX, increased the C max and area under the curve [(AUC) 0-24 h ] of MTX, and inhibited OAT1/3 expression in the kidney and P-gp expression in the small intestine. Conclusions:The findings suggested that there is a drug interaction between WZC and MTX and that OAT1/3 in the kidney and P-gp in the small intestine may be the main targets mediating the drug interaction, and attention should be paid when they are used in combination.

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Analytical methodologies for determination of methotrexate and its metabolites in pharmaceutical, biological and environmental samples

Cited by 61 publications

References 141 publications

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Overview of Dual-Acting Drug Methotrexate in Different Neurological Diseases, Autoimmune Pathologies and Cancers

Relationship Between the Free and Total Methotrexate Plasma Concentration in Children and Application to Predict the Toxicity of HD-MTX

Wuzhi capsule increased systemic exposure to methotrexate by inhibiting the expression of OAT1/3 and P-gp

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