Corpus ID: 43549358

Methotrexate binding to human plasma proteins.

@article{Skibiska1990MethotrexateBT,
  title={Methotrexate binding to human plasma proteins.},
  author={Lidia Skibińska and C. Ramlau and Jerzy Zaluski and Bogdan Olejniczak},
  journal={Polish journal of pharmacology and pharmacy},
  year={1990},
  volume={42 2},
  pages={
          151-7
        }
}
The percentage of methotrexate (MTX) binding to plasma protein was 50.4 +/- 1.9 in healthy subject, and 32.3 +/- 3.6 in patients with cancer (breast carcinoma in most cases). Drugs used in combination with MTX in therapy (vincristine, vinblastine, cyclophosphamide, 5-fluorouracil, prednisone) depress the MTX binding to albumins. MTX binds to two kinds of albumins binding sites, with different binding constants: K1 = 8.88 mM-1 and K2 = 1.76 mM-1. 
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The methodological aspects of protein-ligand interactions, the relationship between protein binding and drug disposition, and the clinical relevance of free drug monitoring in cancer patients are discussed. Expand
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Prediction of methotrexate CNS distribution in different species - influence of disease conditions.
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Investigation of the spatial distribution of unbound methotrexate in healthy rat brain by parallel microdialysis and data on unbound brainECF, CSF and plasma concentrations concluded that advanced mathematical modeling is a most valid approach to develop SBPK models that allow for revealing the mechanisms underlying the relationship between brain ECF and CSF concentrations in health and disease. Expand
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TLDR
Malignant effusions were noticeable only in the disposition phase of MTX resulting in an apparent "third space" and the resulting increase in half-life may be associated with unanticipated toxicity. Expand
Measurement of methotrexate in human cerebrospinal fluid using a chemiluminescence immunoassay intended for serum and plasma matrices
TLDR
This study measured methotrexate (MTX) concentrations in the CSF using a high‐performance liquid chromatography (HPLC) method intended for analyzing CSF matrices and a chemiluminescence immunoassay (CLIA)method intended for assessing serum and plasma matrices. Expand
Urinary coproporphyrin I/(I + III) ratio as a surrogate for MRP2 or other transporter activities involved in methotrexate clearance.
TLDR
The final model indicates that MTXCL was dependent on the change in the ratio between P1 and P3, DIS and creatinine clearance, and it is plausible that it reflects a function modified in response to the drug. Expand
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The aim of the research was to develop a preclinical brain distribution model, allowing the prediction of human brain target site concentrations on the basis of preclinical data, and understanding of time-dependent (also non-steady state) kinetics of the unbound drug in brainECF and CSF is essential. Expand
An Inexpensive, In-House-Made, Microdialysis Device for Measuring Drug-Protein Binding.
An inexpensive, in-house made microdialysis device is described that is suitable for measuring the binding of small molecules including drug candidates to serum proteins or other macromolecules. The… Expand