Abstract
Different tacrolimus epoxides and dihydrodiol epoxides arising from the chemical oxidation of the parent drug are described. Open-chain tautomeric forms involving the lactone function were identified for the tacrolimus epoxides. Moreover, the identification by electrospray and electrospray linked scan mass spectrometry of an SDZ-RAD C16-C27 O-demethyl 17, 18-19, 20-21, 22 tris-epoxide new metabolite isolated from pig liver microsomes is reported. The in vitro immunosuppressive activity, using mixed lymphocyte reactions of the two macrolide reported oxidation compounds are discussed.
Copyright 2001 John Wiley & Sons, Ltd.
MeSH terms
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Animals
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Biotransformation
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Cells, Cultured
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Chromatography, High Pressure Liquid / methods
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Everolimus
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Humans
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Immunosuppressive Agents / pharmacokinetics
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Immunosuppressive Agents / pharmacology
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Lactones / chemistry
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Lymphocyte Culture Test, Mixed
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Lymphocytes / drug effects
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Lymphocytes / immunology*
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Microsomes, Liver / metabolism*
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Models, Molecular
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Molecular Conformation
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NADP / metabolism
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Oxidation-Reduction
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Sirolimus / analogs & derivatives*
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Sirolimus / chemistry
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Sirolimus / pharmacokinetics*
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Sirolimus / pharmacology*
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Spectrometry, Mass, Electrospray Ionization / methods
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Stereoisomerism
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Swine
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Tacrolimus / chemistry
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Tacrolimus / pharmacokinetics*
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Tacrolimus / pharmacology*
Substances
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Immunosuppressive Agents
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Lactones
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NADP
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Everolimus
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Sirolimus
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Tacrolimus