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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1983-5-27
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pubmed:abstractText |
The toxicology and pharmacology of formycin both as a single agent and combined with the adenosine deaminase inhibitor 2'-deoxycoformycin (dCF) were examined in outbred Swiss mice heterozygous for the nude gene (nu/+). The LD10 for formycin alone given on a daily x 5 schedule was 21 mg/kg. When the animals were pretreated with 1 mg/kg of dCF 1 hour prior to each dose of formycin, toxicity was approximately doubled, ie, LD10 was reduced to 10 mg/kg. Death was associated with hepatic toxicity in both treatment regimens; suppression of leukocyte counts was mild except at doses greater than the LD10. Formycin nucleotides were detected by high-performance liquid chromatography in the livers of mice treated with formycin either alone or combined with dCF. When isolated rat hepatocytes were incubated for 2 hours with either formycin or dCF plus formycin, analog nucleotides accumulated in the cells. Cellular ATP decreased to below the limits of detection, whereas a large peak corresponding to formycin-5'-triphosphate was present. This replacement of cellular ATP by formycin-5'-triphosphate may help explain the hepatic toxicity observed.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenosine Deaminase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Aspartate Aminotransferases,
http://linkedlifedata.com/resource/pubmed/chemical/Bilirubin,
http://linkedlifedata.com/resource/pubmed/chemical/Blood Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Coformycin,
http://linkedlifedata.com/resource/pubmed/chemical/Creatine,
http://linkedlifedata.com/resource/pubmed/chemical/Formycins,
http://linkedlifedata.com/resource/pubmed/chemical/Pentostatin,
http://linkedlifedata.com/resource/pubmed/chemical/Ribonucleosides,
http://linkedlifedata.com/resource/pubmed/chemical/formycin
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0361-5960
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
67
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
267-74
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:6600968-Adenosine Deaminase Inhibitors,
pubmed-meshheading:6600968-Animals,
pubmed-meshheading:6600968-Antibiotics, Antineoplastic,
pubmed-meshheading:6600968-Aspartate Aminotransferases,
pubmed-meshheading:6600968-Bilirubin,
pubmed-meshheading:6600968-Blood Glucose,
pubmed-meshheading:6600968-Blood Urea Nitrogen,
pubmed-meshheading:6600968-Coformycin,
pubmed-meshheading:6600968-Creatine,
pubmed-meshheading:6600968-Drug Synergism,
pubmed-meshheading:6600968-Female,
pubmed-meshheading:6600968-Formycins,
pubmed-meshheading:6600968-Lethal Dose 50,
pubmed-meshheading:6600968-Liver,
pubmed-meshheading:6600968-Male,
pubmed-meshheading:6600968-Mice,
pubmed-meshheading:6600968-Mice, Mutant Strains,
pubmed-meshheading:6600968-Mice, Nude,
pubmed-meshheading:6600968-Pentostatin,
pubmed-meshheading:6600968-Rats,
pubmed-meshheading:6600968-Ribonucleosides
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pubmed:year |
1983
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pubmed:articleTitle |
Biochemical pharmacology and toxicology of formycin alone and in combination with 2'-deoxycoformycin (pentostatin).
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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