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  • Title: Some observations on the human pharmacology of methotrexate.
    Author: Calvert AH, Bondy PK, Harrap KR.
    Journal: Cancer Treat Rep; 1977 Dec; 61(9):1647-56. PubMed ID: 597817.
    Abstract:
    Plasma and urinary levels of methotrexate (MTX) have been measured enzymatically in 18 patients receiving doses of 5-1250 mg. When tritium-labeled MTX was administered, plasma levels measured by radioisotope counting were significantly higher than those measured enzymatically, the difference being accounted for by the presence of tritium label in plasma water as a result of drug metabolism. Renal clearance of MTX correlated well with glomerular filtration rate (GFR) and was consistently lower than the GFR, suggesting tubular reabsorption of the drug at the rate of urine flow studied. Plasma clearance measured by an infusion method was consistently greater than renal clearance, suggesting drug metabolism. Biliary MTX levels have been measured in three patients and are very much higher than plasma levels, suggesting a quantitatively important biliary recirculation of the drug. Plasma levels of MTX measured after 24 hours were not significantly different following iv or im administration, but were higher if an infusion was used.
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