Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates.

@article{Kremer1986MethotrexateMA,
  title={Methotrexate metabolism analysis in blood and liver of rheumatoid arthritis patients. Association with hepatic folate deficiency and formation of polyglutamates.},
  author={Joel M. Kremer and John Galivan and Anita Streckfuss and Barton A. Kamen},
  journal={Arthritis and rheumatism},
  year={1986},
  volume={29 7},
  pages={
          832-5
        }
}
Serum and red blood cell methotrexate (MTX) levels, as well as hepatic levels of MTX and folate, were analyzed in 24 patients who had received long-term oral MTX weekly for the treatment of rheumatoid arthritis. The serum MTX level peaked rapidly and was insignificant after 24 hours. The red blood cell MTX level was not related to the interval from the last MTX dose. In hepatic tissue obtained by liver biopsy, MTX was found in a predominantly polyglutamated form with depleted hepatic folate… Expand
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To better define the effects of chronic MTX treatment, tissue levels of MTX, MTXGlun, and folate were measured in three monkeys treated with weekly intramuscular MTX for 1 year and greater than 80% of the total tissue MTX found was in the form of polyglutamated derivatives. Expand
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Analysis of variance demonstrated that the specific activity of the enzyme system in lymphocytes was significantly lower in the MTX-treated group, with an activity approximately one-half that of the control and the non-MTX- treated groups. Expand
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This article evaluates the relationship between the pharmacokinetics of methotrexate (MTX), its efficacy in the treatment of rheumatoid arthritis (RA), and serum folic acid (FA) levels. TheExpand
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References

SHOWING 1-10 OF 17 REFERENCES
Methotrexate Accumulation and Folate Depletion in Cells as a Possible Mechanism of Chronic Toxicity to the Drug
TLDR
It is proposed that persistent metotrexate concentrations and/or the associated folate deficiency may be related to the toxicity of methotrexate, especially in time of cellular stress. Expand
Methotrexate hepatotoxicity in psoriasis. Consideration of liver biopsies at regular intervals.
TLDR
Age of the patient and duration of therapy have been found to be significant factors in those patients receiving only the weekly oral dosage schedule and fibrosis of the liver developed to a degree that contraindicated further treatment with methotrexate. Expand
Hepatotoxicity of methotrexate in the treatment of psoriasis.
Fifty patients with psoriasis were evaluated prospectively and retrospectively for possible hepatotoxicity from methotrexate therapy. Liver function studies were not reliable indicators of pathologicExpand
The safety and efficacy of the use of methotrexate in long-term therapy for rheumatoid arthritis.
TLDR
Toxicity was noted at some time in 26 of 29 patients (90%), but reactions universally became mild and tolerable after adjustment of the dosage, and there was a significant reduction in mean prednisone dosage. Expand
Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics.
  • A. Nyfors
  • Medicine, Biology
  • Acta pathologica et microbiologica Scandinavica. Section A, Pathology
  • 1977
TLDR
Comparison of a material A and B indicates that the prevalence of cirrhosis and fibrosis among MTX treated psoriatics increases rapidly beyond a cumultative dose of two to four grams of MTX. Expand
Morphogenesis of fibrosis and cirrhosis in methotrexate‐treated patients with psoriasis
TLDR
The study revealed liver damage commencing with small foci of piecemeal necrosis, followed by the destruction of the limiting plate and the occurrence of stellate periportal fibrosis, and the pathogenesis of the development of fibrosis and cirrhosis is mixed in some cases. Expand
Methotrexate and folate content of erythrocytes in patients receiving oral vs intramuscular therapy with methotrexate.
TLDR
1. Farrell RL, Roling GT, Castell DO: Stimulation of the incompetent lower esophageal sphincter: A possible advance in therapy of heartburn. Expand
Hepatic parenchymal cell glutamylation of methotrexate studied in monolayer culture.
TLDR
The results demonstrate limited capacity of the hepatocytes to glutamylate longer chain length polyglutamate derivatives, and this process is impaired by addition of folinic acid to the medium. Expand
Analysis of methotrexate polyglutamate derivatives in vivo.
TLDR
The I-60 column is placed in line with the U6K injector and the M45 solvent delivery system with a guard column, and appears to retain the lower chain length methotrexate derivatives. Expand
A rapid, radiochemical-ligand binding assay for methotrexate.
TLDR
A radiochemical ligand binding assay for methotrexate is provided and contemplates both direct and sequential assay techniques, and it is not interfered with by vast excesses of many natural folate derivatives. Expand
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