AIMS: Pemigatinib, an inhibitor of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases, is approved for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma. Pemigatinib is predominantly metabolized by CYP3A4 with minimal renal elimination. METHODS: Separate hepatic and renal impairment studies were conducted to evaluate the effect of these impairments on pemigatinib pharmacokinetics (PK). Each study was of open-label, parallel-group design, conducted in participants with normal organ function and with hepatic or renal impairment. Plasma concentrations of pemigatinib were quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pemigatinib PK parameters were derived by noncompartmental analysis. Geometric mean ratios and two-sided 90% confidence intervals of Cmax , AUC0-t , and AUC0-∞ were compared by analysis of variance (ANOVA). RESULTS: Compared with healthy matched participants: Cmax and AUC0-∞ ratio (90% confidence interval) in participants with moderate hepatic impairment were 96.7% (59.4%, 157%) and 146% (100%, 212%), respectively; Cmax and AUC0-∞ ratio in participants with severe hepatic impairment were 94.2% (68.9%, 129%) and 174% (116%, 261%), respectively; Cmax and AUC0-∞ ratio in participants with severe renal impairment were 64.6% (44.1%, 94.4%) and 159% (95.4%, 264%), respectively; Cmax and AUC0-∞ ratio in participants with end-stage renal disease (ESRD) before haemodialysis (HD) were 77.5% (51.2%, 118%) and 76.8% (54.0%, 109%), respectively; Cmax and AUC0-∞ ratio in participants with ESRD after HD were 90.0% (59.3%, 137%) and 91.3% (64.1%, 130%), respectively. CONCLUSION: Pemigatinib dose should be reduced for patients with severe hepatic or renal impairment, and no dose adjustment is required for patients with moderate hepatic impairment or in ESRD patients undergoing HD.
AIMS: Pemigatinib, an inhibitor of the fibroblast growth factor receptor (FGFR) family of receptor tyrosine kinases, is approved for previously treated, unresectable locally advanced or metastatic cholangiocarcinoma. Pemigatinib is predominantly metabolized by CYP3A4 with minimal renal elimination. METHODS: Separate hepatic and renal impairment studies were conducted to evaluate the effect of these impairments on pemigatinib pharmacokinetics (PK). Each study was of open-label, parallel-group design, conducted in participants with normal organ function and with hepatic or renal impairment. Plasma concentrations of pemigatinib were quantified by liquid chromatography tandem mass spectrometry (LC-MS/MS) and pemigatinib PK parameters were derived by noncompartmental analysis. Geometric mean ratios and two-sided 90% confidence intervals of Cmax , AUC0-t , and AUC0-∞ were compared by analysis of variance (ANOVA). RESULTS: Compared with healthy matched participants: Cmax and AUC0-∞ ratio (90% confidence interval) in participants with moderate hepatic impairment were 96.7% (59.4%, 157%) and 146% (100%, 212%), respectively; Cmax and AUC0-∞ ratio in participants with severe hepatic impairment were 94.2% (68.9%, 129%) and 174% (116%, 261%), respectively; Cmax and AUC0-∞ ratio in participants with severe renal impairment were 64.6% (44.1%, 94.4%) and 159% (95.4%, 264%), respectively; Cmax and AUC0-∞ ratio in participants with end-stage renal disease (ESRD) before haemodialysis (HD) were 77.5% (51.2%, 118%) and 76.8% (54.0%, 109%), respectively; Cmax and AUC0-∞ ratio in participants with ESRD after HD were 90.0% (59.3%, 137%) and 91.3% (64.1%, 130%), respectively. CONCLUSION: Pemigatinib dose should be reduced for patients with severe hepatic or renal impairment, and no dose adjustment is required for patients with moderate hepatic impairment or in ESRD patients undergoing HD.