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New study links in vitro data with mixed effects modelling to assess DDI potential
Date: 07 Apr 2009
A paper published in the journal Pharmaceutical Statistics presents a new framework for the quantification of metabolic drug-drug interactions (mDDIs) using in vitro data in combination with mixed effects modelling.
Scientists at Simcyp and Pfizer initially simulated in vivo mDDIs from in vitro data using the Simcyp Population-based ADME Simulator. These in silico results, which incorporate population variability, accurately reflected both the mean and the range of mDDI magnitudes observed in clinical studies. These simulated data were subsequently used in non-linear mixed effect modelling (NONMEM®) to test the power of these studies to identify mDDIs. A thorough account of the methodology is presented in the paper.
The study highlighted several elements which can influence the outcome of DDI studies, including the number of patients receiving concomitant medication, the magnitude of the interaction to be quantified, the potency and dose of the inhibitor, and the importance of the inhibited metabolic pathway to the substrate’s overall metabolic fate. However, the group’s findings increase confidence in mixed effect modelling approaches to appropriately quantify ‘true’ interactions and emphasize the value of using simulated data in clinical trial design.
The article, by Johnson et al., is entitled, ‘Assessing the efficiency of mixed effects modelling in quantifying metabolism based drug-drug interactions: using in vitro data as an aid to assess study power.’
Please click here for a link to the abstract and full text options.