maraviroc in vitro assessment of drugdrug interaction potential aims to characterize the cytochrome p450 enzymes responsible for the ndealkylation of maraviroc in vitro and predict the extent of clinical drugdrug interactions ddismethods human liver and recombinant cyp microsomes were used to identify the cyp enzyme responsible for maraviroc ndealkylation studies comprised enzyme kinetics and evaluation of the effects of specific cyp inhibitors in vitro data were then used as inputs for simulation of ddis with ketoconazole ritonavir saquinavir and atazanvir using the simcyptrade mark populationbased absorption distribution metabolism and elimination adme simulator study designs for simulations mirrored those actually used in the clinicresults maraviroc was metabolized to its ndealkylated product via a single cyp enzyme characterized by a km of 21 microm and vmax of 045 pmol pmol1 min1 in human liver microsomes and was inhibited by ketoconazole cyp3a4 inhibitor in a panel of recombinant cyp enzymes cyp3a4 was identified as the major cyp responsible for maraviroc metabolism using recombinant cyp3a4 ndealkylation was characterized by a km of 13 microm and a vmax of 3 pmol pmol1 cyp min1 simulations therefore focused on the effect of cyp3a4 inhibitors on maraviroc pharmacokinetics the simulated median auc ratios were in good agreement with observed clinical changes within twofold in all cases although in general there was a trend for overprediction in the magnitude of the ddiconclusion maraviroc is a substrate for cyp3a4 and exposure will therefore be modulated by cyp3a4 inhibitors simcyptrade mark has successfully simulated the extent of clinical interactions with cyp3a4 inhibitors further validating this software as a good predictor of cypbased ddis