Absorption, Metabolism and Excretion of Surufatinib in Rats and Humans

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 [C-14] 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 T-max of 4 hours post-dose. The estimated t(1/2) appeared longer in humans than in rats (mean t(1/2): 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.