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Research ArticleArticle

THE PHYSIOLOGICAL DISPOSITION OF DICHLOROMETHOTREXATE-Cl36 IN ANIMALS

Vincent T. Oliverio and Jack D. Davidson
Journal of Pharmacology and Experimental Therapeutics July 1962, 137 (1) 76-83;
Vincent T. Oliverio
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Jack D. Davidson
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Abstract

The distribution, excretion, and metabolism of radioactive dichloromethotrexate (DCM-Cl36) following single parenteral and oral doses in the mouse, rat, rabbit and dog have been studied.

One hour following parenteral administration in mice, radioactivity was present in all tissues and organs examined but was predominantly concentrated in the liver, small intestine including its contents, and the kidneys.

In 48-hour studies, following parenteral dosage, two-thirds of the radioactivity was recovered in the feces and approximately one-third in the urine. The liver, with about 1% of the dose, was the only organ to contain a measurable quantity of the drug. In contrast, following oral adminis-tration more than 90% of the radioactivity was excreted in the bile and gastrointestinal tract. The excretion pattern in L1210 tumorearing mice was not significantly different from that in normal mice.

Approximately complete recoveries of the radioactive dose were obtained in both mouse and rat 48-hour urinary and fecal excretion studies.

Following various single parenteral dosages of DCM-Cl36, the total amount of radioactivity recovered from bile plus urine was approximately the same in all species with slight variations occurring in the amount excreted during the early hours.

All urine, fecal and bile samples were subjected to DEAE cellulose column chromatography and the eluted compounds were characterized by their ultraviolet spectral absorption. DCM-Cl36 was eluted at its customary spot and only one metabolite, 4-deamino-4,7-dihydroxy DCM-Cl36 was detected.

DCM-Cl36 was metabolized to variable extents in the three rodent species but was excreted unchanged in the dog.

Footnotes

    • Received February 27, 1962.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 137, Issue 1
1 Jul 1962
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Research ArticleArticle

THE PHYSIOLOGICAL DISPOSITION OF DICHLOROMETHOTREXATE-Cl36 IN ANIMALS

Vincent T. Oliverio and Jack D. Davidson
Journal of Pharmacology and Experimental Therapeutics July 1, 1962, 137 (1) 76-83;

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Research ArticleArticle

THE PHYSIOLOGICAL DISPOSITION OF DICHLOROMETHOTREXATE-Cl36 IN ANIMALS

Vincent T. Oliverio and Jack D. Davidson
Journal of Pharmacology and Experimental Therapeutics July 1, 1962, 137 (1) 76-83;
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