Abstract Ubrogepant is a calcitonin gene–related peptide receptor antagonist approved for the acute treatment of migraine with or without aura in adults. The mass balance and metabolism of ubrogepant was evaluated in six healthy male adults administered a single oral dose of 14 C‐ubrogepant 50 mg (∼200 µCi). Overall, the mean total radioactivity recovery was 92.4% (95% CI: 77.8%‐107%) of the administered dose, with 82.9% in feces (95% CI: 66.7%‐99.1%) and 9.52% in urine (95% CI: 7.78%‐11.3%). Ubrogepant was eliminated mainly via metabolism, primarily via biliary/fecal excretion. Approximately 42% and 6% of the dose was excreted as unchanged parent drug in feces and urine, respectively. The major circulating components of drug‐related material (DRM) in pooled plasma samples were ubrogepant (55%), M15 (13%), and M20 (3.5%). M15 (glucuronide of methylated catechol) and M20 (glucuronide of mono‐oxygenated ubrogepant M8) also were the main metabolites in urine, together representing about 2% of DRM. In feces, the main metabolites were the oxidative metabolites M6 (di‐oxygenated ubrogepant) and M8, together representing about 29% of DRM. In vitro assays showed that ubrogepant metabolism occurs predominantly via CYP3A4.
Boinpally et al. (Thu,) studied this question.