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

Effect of bisphenol A on drug-metabolizing enzyme activities by human hepat ic cytochrome P450s (CYP) was investigated. We measured aminopyrine N-demet hylation by eleven kinds of cDNA-expressed CYPs, CYP2C19 and CYP2B6 catalyz ed most efficiently the aminopyrine N-demethylation, followed by CYP2C8 and CYP2D6. Bisphenol A (1 mM) most efficiently inhibited aminopyrine N-demeth ylation by CYP2C8 and CYP2C19 by 82% and 85%, respectively, whereas inhibit ion of the activities by CYP 2B6 and 2D6 was less than 40%. Bisphenol A exh ibited a noncompetitive-type inhibition of aminopyrine N-demethylase activi ty by CYP2C8 with K-i value of 97 mu M. Additionally, we investigated the i nhibitory effect of bisphenol A on CYP2C19-mediated S-mephenytoin 4-hydroxy lation. Bisphenol A exhibited a mixed-type inhibition with K-i value of 113 mu M. These results suggest that bisphenol A inhibits human hepatic CYP ac tivities, especially CYP2C8 and CYP2C19.