In vivo approach for the evaluation of mechanism-based inhibition of cytochrome P450 3A in rats

@inproceedings{Sekiguchi2008InVA,
  title={In vivo approach for the evaluation of mechanism-based inhibition of cytochrome P450 3A in rats},
  author={Nobuo Sekiguchi and Motohiro Kato and Maiko Takada and Hideo Watanabe and Atsuko Higashida and Shogo Sakai and Masaki Ishigai and Yoshinori Aso},
  year={2008}
}
1. There have been no reports showing that the area under the concentration-time curve (AUC) of a probe drug is elevated due to mechanism-based inhibition (MBI) of drug-metabolizing enzymes in animals. This study ascertained that mechanism-based inhibitors reported to induce drug–drug interactions (DDIs) in humans also caused MBI in rats.2. Midazolam (MDZ), mainly metabolized by cytochrome P450 3A in rats, and mibefradil, which showed the most intense time-dependent inhibition among the… CONTINUE READING