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rdf:type |
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lifeskim:mentions |
umls-concept:C0014442,
umls-concept:C0020792,
umls-concept:C0025519,
umls-concept:C0026030,
umls-concept:C0034493,
umls-concept:C0034693,
umls-concept:C0034721,
umls-concept:C0059563,
umls-concept:C0086418,
umls-concept:C0205164,
umls-concept:C0729218,
umls-concept:C0870883,
umls-concept:C1273518,
umls-concept:C1533691
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pubmed:issue |
2
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pubmed:dateCreated |
1992-5-15
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pubmed:abstractText |
The metabolism of the immunosuppressant FK-506 was shown to be catalyzed primarily by cytochrome P450 isozymes of the P450 3A subfamily. Antibodies against rat P450 3A inhibited FK-506 metabolism by 82% in rat liver microsomes and by 35-56% in liver microsomes from humans, dexamethasone-induced rats, and erythromycin-induced rabbits. Poor species cross-reactivity of the antibodies, metabolic switching, and/or some metabolism by P450 isozymes other than P450 3A may be responsible for the incomplete inhibition observed. Besides anti-rat P450 3A, antibodies against rat P450 1A also appeared to have some inhibitory effect implicating these particular cytochrome P450 isozymes as having a minor role in FK-506 metabolism. The formation of 13-desmethyl FK-506, identified here as a major metabolite of FK-506 in all types of microsomes examined, was inhibited completely by anti-P450 3A in liver microsomes from dexamethasone-induced rats and erythromycin-induced rabbits but only partially in human and control rat liver microsomes.
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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 |
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0003-9861
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
294
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
454-60
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:1373595-Adult,
pubmed-meshheading:1373595-Animals,
pubmed-meshheading:1373595-Antibodies,
pubmed-meshheading:1373595-Biotransformation,
pubmed-meshheading:1373595-Carbon Radioisotopes,
pubmed-meshheading:1373595-Cytochrome P-450 CYP2E1,
pubmed-meshheading:1373595-Cytochrome P-450 Enzyme System,
pubmed-meshheading:1373595-Dexamethasone,
pubmed-meshheading:1373595-Female,
pubmed-meshheading:1373595-Humans,
pubmed-meshheading:1373595-Kinetics,
pubmed-meshheading:1373595-Male,
pubmed-meshheading:1373595-Microsomes, Liver,
pubmed-meshheading:1373595-Mixed Function Oxygenases,
pubmed-meshheading:1373595-Proadifen,
pubmed-meshheading:1373595-Rabbits,
pubmed-meshheading:1373595-Rats,
pubmed-meshheading:1373595-Rats, Inbred Strains,
pubmed-meshheading:1373595-Tacrolimus,
pubmed-meshheading:1373595-Troleandomycin
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pubmed:year |
1992
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pubmed:articleTitle |
In vitro metabolism of FK-506 in rat, rabbit, and human liver microsomes: identification of a major metabolite and of cytochrome P450 3A as the major enzymes responsible for its metabolism.
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pubmed:affiliation |
Department of Animal and Exploratory Drug Metabolism, Merck Sharp & Dohme Research Laboratories, New Jersey 07065.
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pubmed:publicationType |
Journal Article
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