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Significance of variation in serum thymidine concentration for the marrow toxicity of methotrexate.

Abstract：

:Thymidine (dThd) concentrations have been measured in the sera of normal subjects and solid tumor cancer patients by means of a sensitive high-pressure liquid chromatographic assay to determine whether natural and methotrexate (MTX)-induced fluctuations were large enough to alter the toxicity of MTX to marrow. The mean concentration in normal subjects with measurable levels was 1.3 X 10(-7) M (range less than 4 X 10(-8) to 6 X 10(-7) M). In cancer patients it was 2.0 X 10(-7) M (range less than 4 X 10(-8) to 8.7 X 10(-7)), and in malignant effusions 1.2 X 10(-7) M (range less than 4 X 10(-8) to 2.2 X 10(-7) M). The wide range of variation in random samples was also found when multiple samples were obtained from the same patient during a 24-h period where dThd concentration varied from a minimum of two- to greater than six-fold. Treatment with MTX 3 mg/m2 caused an average 59% reduction in serum dThd during the first 24 h after injection during nine courses of therapy. dThd was tested for its ability to modulate the toxicity of MTX to human granulocate colony-forming units in culture across the concentration range found in vivo: changes in dThd concentration equivalent to normal fluctuations in vivo altered colony survival by 31% to greater than 72%. A reduction in culture dThd equivalent to that produced in vivo by high-dose TMX increased colony kill by 25%. The results indicate that in vivo variations in serum dThd are in an appropriate range and of a sufficient magnitude to alter the toxicity of MTX to marrow, and they demonstrate that MTX can modulate its own toxicity by reducing serum dThd.

journal_name

Cancer Chemother Pharmacol

journal_title

Cancer chemotherapy and pharmacology

authors

Howell SB,Mansfield SJ,Taetle R

doi

10.1007/BF00434388

subject

Has Abstract

pub_date

1981-01-01 00:00:00

pages

221-6

issue

4

eissn

0344-5704

issn

1432-0843

journal_volume

5

pub_type

杂志文章

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