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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
7
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pubmed:dateCreated |
1984-9-19
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pubmed:abstractText |
The metabolism of doxorubicin (A), 4'-epidoxorubicin (E) and 4'-deoxydoxorubicin (D) was studied in vitro by incubating the analogs with rat liver subcellular fractions and in vivo by chromatographic analysis of human urine. Metabolites were identified by high-pressure liquid chromatography, fluorescence spectroscopy and enzymatic conversion. Human urine contained unchanged drug as well as the corresponding alcohol metabolites in all cases; however, urine of patients who received E also contained two glucuronides which could not be detected in the urine of patients who received A or D. We have identified these glucuronides as 4'-epidoxorubicin glucuronide (E-Glu) and 4'-epidoxorubicinol glucuronide (Eol-Glu). It was concluded that the glucuronide moiety is linked to the daunosamine sugar at the C4'-OH position. A hypothesis is proposed that this glucuronidation pathway may explain the differences in pharmacokinetics and toxicity between E and A. Rat liver microsomes were found to convert all three drugs to the 7-deoxyaglycones at the same rate. Rat liver 100,000 g supernatant was found to be capable of converting these drugs to their respective alcohol metabolites, doxorubicinol (Aol) being formed somewhat slower than 4'-epidoxorubicinol (Eol) and 4'-deoxydoxorubicinol (Dol).
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4'-deoxydoxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Antibiotics, Antineoplastic,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Epirubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Glucuronates
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0277-5379
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
20
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
919-26
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:6589165-Animals,
pubmed-meshheading:6589165-Antibiotics, Antineoplastic,
pubmed-meshheading:6589165-Antineoplastic Agents,
pubmed-meshheading:6589165-Chromatography, High Pressure Liquid,
pubmed-meshheading:6589165-Doxorubicin,
pubmed-meshheading:6589165-Epirubicin,
pubmed-meshheading:6589165-Glucuronates,
pubmed-meshheading:6589165-Humans,
pubmed-meshheading:6589165-Liver,
pubmed-meshheading:6589165-Male,
pubmed-meshheading:6589165-Rats,
pubmed-meshheading:6589165-Rats, Inbred Strains
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pubmed:year |
1984
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pubmed:articleTitle |
Metabolism of 4'-modified analogs of doxorubicin. unique glucuronidation pathway for 4'-epidoxorubicin.
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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