PMID- 34282472 OWN - NLM STAT- MEDLINE DCOM- 20220203 LR - 20220203 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 77 IP - 12 DP - 2021 Dec TI - Evaluation of drug-drug interactions of pemigatinib in healthy participants. PG - 1887-1897 LID - 10.1007/s00228-021-03184-z [doi] AB - PURPOSE: Pemigatinib (INCB054828), a potent and selective oral fibroblast growth factor receptor 1-3 inhibitor, is a Biopharmaceutical Classification System class II compound with good permeability and pH-dependent solubility that is predominantly metabolized by cytochrome P450 (CYP) 3A. Two drug-drug interaction studies, one with acid-reducing agents, esomeprazole (proton pump inhibitor [PPI]) and ranitidine (histamine-2 [H2] antagonist), and the other with potent CYP3A-modulating agents, itraconazole (CYP3A inhibitor) and rifampin (CYP3A inducer), were performed. METHODS: Both were open-label, fixed-sequence studies conducted in up to 36 healthy participants each, enrolled into two cohorts (n = 18 each). Pemigatinib plasma concentration was measured, and pharmacokinetic parameters were derived by non-compartmental analysis. RESULTS: There was an 88% and 17% increase in pemigatinib area under the plasma drug concentration-time curve (AUC) and maximum plasma drug concentration (C(max)), respectively, with itraconazole, and an 85% and 62% decrease in pemigatinib AUC and C(max) with rifampin coadministration. There was a 35% and 8% decrease in pemigatinib AUC and C(max), respectively, with esomeprazole, and a 2% decrease in C(max) and 3% increase in AUC with ranitidine coadministration. In both studies, all adverse events reported were grade