Abstract
Three highly reproducible experiments on drug interaction in normal human volunteers provided anomalous results: chronic halofenate administration shortened plasma antipyrine and bishydroxycoumarin half-lives but prolonged plasma warfarin half-lives. This dissociation in the effect produced by a chronically administered drug on the metabolism of test drugs has not previously been reported in man. Chronic halofenate administration to rats, mice and dogs stimulated several hepatic microsomal drug-metabolizing systems, including those responsible for bishydroxycoumarin warfarin hydroxylation.
MeSH terms
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Adult
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Aldehyde-Lyases / metabolism
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Animals
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Antipyrine / administration & dosage
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Antipyrine / blood*
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Cytochrome P-450 Enzyme System / metabolism
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Depression, Chemical
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Dicumarol / administration & dosage
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Dicumarol / blood*
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Dogs
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Drug Interactions
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Ethylmorphine-N-Demethylase / metabolism
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Glycolates / pharmacology*
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Half-Life
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Halofenate / administration & dosage
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Halofenate / pharmacology*
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Humans
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Male
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Mice
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Microsomes, Liver / enzymology
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Rats
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Stimulation, Chemical
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Time Factors
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Warfarin / administration & dosage
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Warfarin / blood*
Substances
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Glycolates
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Warfarin
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Dicumarol
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Cytochrome P-450 Enzyme System
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Ethylmorphine-N-Demethylase
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Aldehyde-Lyases
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Halofenate
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Antipyrine