TABLE 5

Prediction of VX-509 drug-drug interaction from in vitro parameters of time-dependent inhibition

PrecipitantIn Vitro SystemDonorkinactKIPredicted AUCi/AUCClinical AUCi/AUCa
VX-509HLMsPool 150bbb12
Metabolite (M3)HLMsPool 1500.070.41312
VX-509Human hepatocytesYOW0.082.42112
VX-509Human hepatocytesHH10070.021.31812
VX-509Human hepatocytesBPB0.025.21012
VX-509Human hepatocytesHu81230.024.9912
VX-509Human hepatocytesHH80040.024.9912
  • AUCi/AUC, fold-change in clinical plasma exposure of midazolam when coadministered with an inhibitor (AUCi), relative to the control state (AUC).

  • a Midazolam substrate.

  • b No detectable TDI.