Background: Surufatinib is a potent small-molecule tyrosine kinase inhibitor and exhibited significant
efficacy in the treatment of neuroendocrine tumors in clinical trials.
Objective: The absorption, metabolism and excretion of surufatinib were investigated in rats and human volunteers
following a single oral dose of [14C] surufatinib.
Methods: The radioactivity was measured in plasma, urine, feces and bile by liquid scintillation counting, and the
metabolites were characterized by liquid chromatography coupled to mass spectrometry.
Results: Surufatinib was orally absorbed similarly in rats and human volunteers, with the median Tmax of 4 hours
post-dose. The estimated t1/2 appeared longer in humans than in rats (mean t1/2: 3.12 hour for male rats, 6.48 hours for
female rats and 23.3 hours for male human volunteers). The excretion of surufatinib was almost complete in rats and
human volunteers in the studies, with the total radioactivity recovery of >90% of the dose. Similarly, in rats and
humans, fecal excretion predominated (approximately 87% of the dose recovered in feces and only 5% in urine). The
parent drug was the major radioactive component detected in the plasma extracts of rats and humans, and no single
circulating metabolite accounted for >10% of the total radioactivity. Unchanged drug was a minor radioactive
component in the excreta of rats and humans.
Conclusion: Fecal excretion was the predominant way for the elimination of surufatinib and its metabolites in rats
and humans. No disproportionate circulating metabolite was observed in humans.