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Simcyp simulations in "close agreement" with outcome of clinical study
Date: 27 Nov 2007
A recent paper, published in the European Journal of Clinical Pharmacology, describes the Simcyp Population-based ADME Simulator as a “powerful tool during early clinical development” when assessing and designing studies on metabolic drug interactions. The research was undertaken by scientists at Roche, Genentech and OSI Pharmaceuticals who were investigating the pharmacokinetics of the well known antitumour agent, erlotinib (commonly known by its trade name Tarciva).
Simcyp simulations were carried out using in vitro data to predict the relative contribution of different enzymes to erlotinib metabolism. These simulations predicted that CYP3A4 contributed to approximately 70% of metabolic elimination, with CYP1A2 responsible for the remaining 30%. A two-fold increase in erlotinib exposure in the presence of ketoconazole, a potent CYP3A4 inhibitor, was also predicted using the Simcyp Simulator.
These in silico results prompted the group to undertake an in vivo drug-drug interaction study. The results of the Simcyp predictions and the clinical study were found to be “in close agreement”. The authors commented on the usefulness of Simcyp simulations in evaluating the variability of outcome within the population, and also the dose adjustments that are required to avoid major side effects when CYP3A4 inhibitors are co-administered.
The paper, by Rakhit et al., is entitled, ‘The effects of CYP3A4 inhibition on erlotinib pharmacokinetics: computer-based simulation (SimcypTM) predicts in vivo metabolic inhibition.'
Click here for a link to the abstract.