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Amgen study uses Simcyp to assess impact of alternative probe substrates on magnitude of DDI
Date: 18 Mar 2010
A paper to be published in the journal, Drug Metabolism and Disposition, describes research undertaken by Foti et al., to select the most appropriate probe substrate for a clinical drug-drug interaction (DDI) study based upon in silico predictions.
The group, from Amgen, measured the in vitro inhibition potency of twenty known inhibitors of CYP3A4 using eight clinically-relevant CYP3A4 probe substrates and testosterone. Similarities in the results led the authors to assign the probe substrates into four clusters. Literature data was then used to compare the in vivo sensitivities of six clinically relevant probe substrates to midazolam.
Finally, the researchers used the Simcyp Population-based ADME Simulator to predict the in vivo magnitude of CYP3A4 DDI caused by their compound and four of the probe sustrates in order to select the most appropriate substrate for a clinical DDI study.
The paper is entitled ‘Selection of alternative CYP3A4 probe substrates for clinical drug interaction studies using in vitro data and in vivo simulation.’ It is available as an e-pub ahead of print.