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- W2142206952 abstract "Endothelium is a metabolically active secretory tissue and an important barrier for metabolic products. Little is known about its contribution to drug oxidation. We investigated the gene and protein expression and enzyme activity of major cytochrome P450 monooxygenases in cultures of primary human coronary endothelial cells and studied its ability to metabolize verapamil, a commonly and widely prescribed calcium antagonist. Of the total 18 P450 monooxygenases investigated, transcripts for CYP1A1, CYP2A6/7, CYP2A13, CYP2B6/7, CYP2C8, CYP2E1, and CYP2J2 were expressed, albeit at different levels. Furthermore, metabolism of verapamil proceeded predominantly via N-desmethylation and/or N-desalkylation, i.e., production of D-617 [2-(3,4-dimethoxyphenyl)-5-amino-2-isopropylvaleronitrile], D-620 [2-(3,4-dimethoxyphenyl)-5-methylamino-2-isopropylvaleronitrile], and norverapamil; but additional metabolites are the O-demethylated products, D-702 [2-(3,4-dimethoxyphenyl)-8-(4-hydroxy-3-methoxyphenyl)-6-methyl-2-isopropyl-6-azaoctanitrile] and D-703 [O-demethylverapamil; 5-N-(3,4-dimethoxyphenethyl)methylamino-2-(3'-methoxy-4'-hydroxyphenyl)-2-isopropylvaleronitrile]. We show endothelium to express an array of monooxygenases, and in view of its large body distribution, endothelium should be considered in the biotransformation of drugs, particularly when tissue-specific metabolism and/or metabolic inactivation are being investigated." @default.
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- W2142206952 date "2003-07-01" @default.
- W2142206952 modified "2023-10-16" @default.
- W2142206952 title "VERAPAMIL: METABOLISM IN CULTURES OF PRIMARY HUMAN CORONARY ARTERIAL ENDOTHELIAL CELLS" @default.
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- W2142206952 doi "https://doi.org/10.1124/dmd.31.7.888" @default.
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