Inhibition of drug-metabolizing enzyme activity in human hepatic cytochrome P450s by bisphenol A.

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Niwa T, Tsutsui M, Kishimoto K, Yabusaki Y, Ishibashi F, Katagiri M

Inhibition of drug-metabolizing enzyme activity in human hepatic cytochrome P450s by bisphenol A.

Biol Pharm Bull. 2000 Apr;23(4):498-501.

PubMed ID

10784435 [ View in PubMed

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Abstract

Effect of bisphenol A on drug-metabolizing enzyme activities by human hepatic cytochrome P450s (CYP) was investigated. We measured aminopyrine N-demethylation by eleven kinds of cDNA-expressed CYPs. CYP2C19 and CYP2B6 catalyzed most efficiently the aminopyrine N-demethylation, followed by CYP2C8 and CYP2D6. Bisphenol A (1 mM) most efficiently inhibited aminopyrine N-demethylation by CYP2C8 and CYP2C19 by 82% and 85%, respectively, whereas inhibition of the activities by CYP 2B6 and 2D6 was less than 40%. Bisphenol A exhibited a noncompetitive-type inhibition of aminopyrine N-demethylase activity by CYP2C8 with Ki value of 97 microM. Additionally, we investigated the inhibitory effect of bisphenol A on CYP2C19-mediated S-mephenytoin 4-hydroxylation. Bisphenol A exhibited a mixed-type inhibition with Ki value of 113 microM. These results suggest that bisphenol A inhibits human hepatic CYP activities, especially CYP2C8 and CYP2C19.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Aminophenazone	Cytochrome P450 2C19	Protein	Humans	Unknown	Substrate	Details