Abstract
Cytochrome p450-mediated metabolism of GRS (indolinone antiaggregant) and its effects on activities of cytochrome p450 isoenzymes were studied. Inhibition of 6 isomers of cytochrome p450 in human liver microsomes was studied with the use of specific substrates. It was found that human liver cytochrome p450 enzymes could not induce degradation of GRS and that GRS was not an inductor or inhibitor of cytochrome p450 family members 1A2, 2C9, 2C19, 2D6, 2C8, and 3A4. Hence, clinical use of the prospective antiaggregant would not involve the risk of uncontrolled fluctuations in GRS concentrations in the organism because of interactions between the drugs.
Keywords:
GRS; antiaggregant; cytochrome p450; indolinone derivative; metabolism.
MeSH terms
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Animals
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Biotransformation / drug effects
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Cytochrome P-450 CYP1A2 / metabolism
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Cytochrome P-450 CYP2C19 / metabolism
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Cytochrome P-450 CYP2C8 / metabolism
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Cytochrome P-450 CYP2C9 / metabolism
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Cytochrome P-450 CYP2D6 / metabolism
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Cytochrome P-450 CYP3A / metabolism
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Enzyme Assays
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Gene Expression
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Humans
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Kinetics
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Liver / drug effects
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Liver / enzymology
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Microsomes, Liver / drug effects*
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Microsomes, Liver / enzymology
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NADP / metabolism
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Oxindoles / pharmacology*
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Platelet Aggregation Inhibitors / pharmacology*
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Rats
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Verapamil / pharmacology
Substances
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Oxindoles
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Platelet Aggregation Inhibitors
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NADP
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Verapamil
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CYP2C9 protein, human
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Cytochrome P-450 CYP2C9
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CYP1A2 protein, human
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CYP2C19 protein, human
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CYP2C8 protein, human
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Cytochrome P-450 CYP1A2
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Cytochrome P-450 CYP2C19
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Cytochrome P-450 CYP2C8
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Cytochrome P-450 CYP2D6
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human