Absorption, Metabolism and Excretion of Surufatinib in Rats and Humans

Ke Li¹, Sheng Ma^2,5, Liyan Miao^2,5,*, Songhua Fan¹, Bin Pan¹, Weihan Zhang¹, Weiguo Su¹, Yating Xiong³, Zheming Gu³, Lian Guo⁴ and Yang Sai^1,* 

¹Hutchison MediPharma Ltd., Shanghai, China; ²The First Affiliated Hospital of Soochow University, Suzhou, China; ³Jiangsu Value Pharmaceutical Services Co., Ltd., Nanjing, China; ⁴XBL-China, Inc., Nanjing, China; ⁵Institute for Interdisciplinary Drug Research and Translational Sciences, College of Pharmaceutical Sciences, Soochow University, Suzhou, China

Abstract: 

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 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.

Keywords: 

Anticancer drug, pharmacokinetics, absorption, excretion, metabolism, surufatinib.