Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin.

@article{Shin2002InhibitoryEO,
  title={Inhibitory effects of tricyclic antidepressants (TCAs) on human cytochrome P450 enzymes in vitro: mechanism of drug interaction between TCAs and phenytoin.},
  author={J G Shin and Ji-Young Park and Min-Jung Kim and J Shon and Y Kellie Yoon and I Cha and S Lee and Se-wook Oh and S Kim and David A. Flockhart},
  journal={Drug metabolism and disposition: the biological fate of chemicals},
  year={2002},
  volume={30 10},
  pages={1102-7}
}
The ability of tricyclic antidepressants (TCAs) to inhibit phenytoin p-hydroxylation was evaluated in vitro by incubation studies of human liver microsomes and cDNA-expressed cytochrome p450s (p450s). The TCAs tested were amitriptyline, imipramine, nortriptyline, and desipramine. Amitriptyline and imipramine strongly and competitively inhibited phenytoin p-hydroxylation in microsomal incubations (estimated K(i) values of 5.2 and 15.5 micro M, respectively). In contrast, nortriptyline and… CONTINUE READING

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