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Pfizer study uses Simcyp in investigation of midazolam glucuronidation
Date: 20 Apr 2009
A paper published in the British Journal of Clinical Pharmacology sheds further light on the role of Phase II enzymes in the in vivo metabolism of midazolam. The study was undertaken by scientists at Pfizer and the Universities of Sussex and Loughborough, UK.
The group quantified a glucuronide metabolite of midazolam in vivo, confirming previous in vitro observations which indicated a role for UGT1A4 the metabolism of the compound.
The Simcyp Population-based ADME Simulator (Version 8.1) was then used to investigate the relative contributions of CYP3A4, CYP3A5 and UGT1A4 to total hepatic intrinsic clearance of midazolam under various conditions. The results of these simulations illustrated an increased role for UGT1A4-mediated metabolism under CYP3A inhibited conditions.
The article, by Hyland et al., is entitled 'In vitro and in vivo glucuronidation of midazolam in humans.’ Please click here for a link to the abstract and full text options.