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Autoinduction of molibresib metabolism was suspected and confirmed in vitro. Here we report the development of a semimechanistic liver-compartment population PK model using PK data from the FTIH study, which adequately describes the autoinduction of molibresib clearance and the PK of both molibresib and GSK3529246. Covariate analysis indicated body weight had a significant effect on the volume of distribution of molibresib and GSK3529246, and higher levels of aspartate aminotransferase resulted in the lower clearance of GSK3529246. This