Advancements in physiologically based pharmacokinetic modeling for fedratinib: updating dose guidance in the presence of a dual inhibitor of CYP3A4 and CYP2C19.

The updated PBPK model improved description of the observed pharmacokinetics and predicted a low risk of clinically significant DDIs between fedratinib and fluconazole. The quantitative evidence serves as a primary foundation for providing dose guidance in clinical practice for the coadministration of fedratinib with dual CYP3A4 and CYP2C19 inhibitors.