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EJCP paper: Simcyp Simulator used in IVIVE study of zolpidem

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Date: 28 Jan 2010

A paper, to be published in the European Journal of Clinical Pharmacology, describes research using the Simcyp Population-based ADME Simulator which was undertaken at Flinders University in Adelaide, Australia.

The aim of the study was to re-evaluate zolpidem as a mechanism-based inactivator of CYP3A in vitro and assess the potential for in vivo metabolic interactions with CYP3A drugs. The Simcyp Population-based ADME Simulator (Version 8.1) was used to automate the in vitro – in vivo extrapolation and provide time-based assessments for interactions with midazolam, a CYP3A probe. Simulations were performed in virtual populations of healthy volunteers and elderly North European Caucasians.

The authors conclude that zolpidem is a relatively weak mechanism-based inactivator of CYP3A in vitro and that, without conducting a potentially hazardous interaction study using midazolam, the in vitro – in vivo extrapolation assessment provides evidence to exclude zolpidem as a significant perpetrator of mDDIs involving CYP3A.

The paper, by Polasek et al., is entitled, ‘In vitro-in vivo extrapolation of zolpidem as a perpetrator of metabolic interactions involving CYP3A’.

Please click here for a link to the abstract and full text options.

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