N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors.

@article{Schmider1995NdemethylationOA,
  title={N-demethylation of amitriptyline in vitro: role of cytochrome P-450 3A (CYP3A) isoforms and effect of metabolic inhibitors.},
  author={Juergen Schmider and David J Greenblatt and Lisa L. von Moltke and Jerold S. Harmatz and Richard I. Shader},
  journal={The Journal of pharmacology and experimental therapeutics},
  year={1995},
  volume={275 2},
  pages={592-7}
}
Biotransformation of amitriptyline (AMI) to its demethylated product nortriptyline (NT) was studied in vitro with human liver microsomes from four different donors, preselected to reflect a range of metabolic rates. Reaction velocity versus substrate concentration was consistent with a sigmoid Vmax model. Vmax varied from 0.42 to 3.42 nmol/mg/min, Km from 33 to 89 microM AMI. Ketoconazole was a highly potent inhibitor of N-demethylation, with a mean Ki value of 0.11 +/- 0.013 microM (+/- S.D… CONTINUE READING