Metabolism and disposition in rats, dogs, and humans of erdafitinib, an orally administered potent pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor.
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Scheers E, Borgmans C, Keung C, Bohets H, Wynant I, Poggesi I, Cuyckens F, Leclercq L, Mamidi RNVS
Metabolism and disposition in rats, dogs, and humans of erdafitinib, an orally administered potent pan-fibroblast growth factor receptor (FGFR) tyrosine kinase inhibitor.
Xenobiotica. 2021 Feb;51(2):177-193. doi: 10.1080/00498254.2020.1821123. Epub 2020 Sep 20.
- PubMed ID
- 32902324 [ View in PubMed]
- Abstract
This article describes in vivo biotransformation and disposition of erdafitinib following single oral dose of (3)H-erdafitinib and (14)C-erdafitinib to intact and bile duct-cannulated (BC) rats (4 mg/kg), (3)H-erdafitinib to intact dogs (0.25 mg/kg), and (14)C-erdafitinib to humans (12 mg; NCT02692677). Peak plasma concentrations of total radioactivity were achieved rapidly (T(max): animals, 1 h; humans, 2-3 h). Recovery of drug-derived radioactivity was significantly slower in humans (87%, 384 h) versus animals (rats: 91-98%, 48 h; dogs: 81%, 72 h). Faeces was the primary route of elimination in intact rats (95%), dogs (76%), and humans (69%); and bile in BC rats (48%). Renal elimination of radioactivity was relatively low in animals (2-12%) versus humans (19%). Unchanged erdafitinib was major component in human excreta (faeces, 17%; urine, 11%) relative to animals. M6 (O-desmethyl) was the major faecal metabolite in humans (24%) and rats (intact, 46%; BC, 11%), and M2 (O-glucuronide of M6) was the prevalent biliary metabolite in rats (14%). In dogs, besides M6, majority of radioactive dose in faeces was composed of multiple minor metabolites. In humans, unchanged erdafitinib was the major circulating entity. O-demethylation of erdafitinib was the major metabolic pathway in humans and animals.
