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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
1983-4-15
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pubmed:abstractText |
Three recombinant human leukocyte interferons (IFLrA, IFLrD, and a hybrid IFLrA/D) that differ markedly in their antiviral activity in murine L cells were examined for their effects on hepatic microsomal drug metabolism in adult female CD-1 mice. When administered for 1 or 3 consecutive days, IFLrA/D, which exhibited the highest antiviral activity in murine L cells, caused a dose-dependent decrease in cytochrome P-450 content and in the rate of metabolism in vitro of benzo[a]pyrene, hexobarbital, 7-ethoxycoumarin, benzphetamine, and zoxazolamine. The concentration of cytochrome b and the activity of NADPH-cytochrome c reductase were also depressed when IFLrA/D was administered for 3 days. Similar but somewhat smaller changes were observed following treatment of mice with IFLrD, which possessed approximately 1% of the antiviral activity of IFLrA/D in murine L cells. In contrast, IFLrA, which was essentially devoid of antiviral activity in the mouse cell line, failed to depress cytochrome P-450 levels and in vitro drug metabolism activity in a consistent or dose-dependent manner. Cytochrome P-450 content and the in vitro rate of metabolism of benzphetamine and zoxazolamine were maximally depressed 8-24 hr after a single intraperitoneal injection of 1.5 micrograms of interferon per mouse; at this time the interferons were no longer detectable in serum. Near-normal levels of cytochrome P-450 and in vitro drug metabolism activity were restored by 48 hr after a single injection of interferon. Treatment of mice with 1.5 micrograms of IFLrA/D once daily for 3 days prolonged hexobarbital sleeping time but not zoxazolamine paralysis time, whereas neither of these was influenced by treatment with IFLrA or D. The results indicate that an interferon-dependent process reduces the level of microsomal cytochrome P-450 in liver and potentiates the pharmacological actions of certain drugs in mice.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:issn |
0090-9556
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
10
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
579-85
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pubmed:dateRevised |
2004-11-17
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pubmed:meshHeading |
pubmed-meshheading:6130903-Animals,
pubmed-meshheading:6130903-Cytochrome P-450 Enzyme System,
pubmed-meshheading:6130903-Female,
pubmed-meshheading:6130903-Hexobarbital,
pubmed-meshheading:6130903-Humans,
pubmed-meshheading:6130903-Interferon Type I,
pubmed-meshheading:6130903-L Cells (Cell Line),
pubmed-meshheading:6130903-Mice,
pubmed-meshheading:6130903-Microsomes, Liver,
pubmed-meshheading:6130903-Zoxazolamine
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pubmed:articleTitle |
Effects of three recombinant human leukocyte interferons on drug metabolism in mice.
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pubmed:publicationType |
Journal Article
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