PBPK Assists with DDI Prediction Without a Rifampin Study for Cobimetinib
Cobimetinib (Cotellic®), approved by the US FDA in 2015, is a kinase inhibitor for treating advanced melanoma. As in the best practice case of ibrutinib, we generally perform physiologically-based pharmacokinetic (PBPK) simulations with model verification based on CYP3A4 strong inhibitor and inducer clinical data. However, with cobimetinib, which is a CYP3A4/UGT2B7 drug, the sponsor had only conducted a study with itraconazole, a strong CYP3A4 inhibitor. There was no rifampin data available to verify the effect of CYP3A4 inducers.