In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A

@article{Polasek2009InVV,
  title={In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A},
  author={Thomas M. Polasek and Janani S. Sadagopal and David J. Elliot and John O. Miners},
  journal={European Journal of Clinical Pharmacology},
  year={2009},
  volume={66},
  pages={275-283}
}
To evaluate zolpidem as a mechanism-based inactivator of human CYP3A in vitro, and to assess its metabolic interaction potential with CYP3A drugs (in vitro-in vivo extrapolation; IV-IVE). A co- vs. pre-incubation strategy was used to quantify time-dependent inhibition of human liver microsomal (HLM) and recombinant CYP3A4 (rCYP3A4) by zolpidem. Experiments involving a 10-fold dilution step were employed to determine the kinetic constants of inactivation (K I and k inact) and to assess the in… CONTINUE READING