Evaluation of drug-drug interaction potential for pemigatinib using physiologically based pharmacokinetic modeling.

ABSTRACT: Pemigatinib is a potent inhibitor of fibroblast growth factor receptor being developed for oncology indications. It is primarily metabolized by cytochrome P450 (CYP) 3A4, and the ratio of estimated concentration over concentration required for 50% inhibition ratio for pemigatinib as an inhibitor of P-glycoprotein (P-gp), organic cation transporter-2 (OCT2), and multidrug and toxin extrusion protein-1 (MATE1) exceeds the cutoff values established in regulatory guidance. A Simcyp minimal physiologically based pharmacokinetic (PBPK) with advanced dissolution, absorption, and metabolism absorption model for pemigatinib was developed and validated using observed clinical pharmacokinetic (PK) data and itraconazole/rifampin drug-drug interaction (DDI) data. The model accurately predicted itracona

SUBMITTER: Ji T 

PROVIDER: S-EPMC9286713 | biostudies-literature | 2022 Jul

REPOSITORIES: biostudies-literature