Establishment of a rat model of diarrhea induced by Surufatinib (B04)

Introduction: Surufatinib is a novel oral small-molecule TKI for the treatment of advanced neuroendocrine tumors. However, diarrhea is a common adverse event of surufatinib which can affects patients’ quality of life and clinical efficacy. Currently, there are no available animal models to study the cause and treatmen of surufatinib-related diarrhea.

Aim(s): The purpose is to establish a rat model of surufatinib-induced diarrhea and to preliminarily investigate the pathological changes.

Materials and methods: Surufatinib (a suspension formulated in 0.5% carboxymethyl cellulose) is formulated into three concentrations: 0.6%, 0.9%, and 1.1%. Forty rats (aged 6 to 8 weeks and weighting between 211g and 231g) were randomly divided into four groups. The control group was given 10 ml/kg of carboxymethyl cellulose by gavage daily, and experimental group was given three concentrations of surufatinib suspension daily, with doses of 60 mg/kg, 90 mg/kg, 110 mg/kg.

Results: The rats in the control group had no diarrhea. And the diarrhea rates of rats in the experimental groups were 20% (60mg/kg group), 50% (90mg/kg group), and 80% (110mg/kg group). The plasma levels of DAO and D-lactate in the surufatinib highest dose group rats were significantly elevated compared to the other groups, suggesting a disruption in intestinal barrier function.Histopathological examination indicated that the damaged organ was the colon of rats.

Conclusion: We established a rat model of surufatinib-induced diarrhea, the rate of diarrhea in rats can reach 80% at a dose of 110 mg/kg. It would be a useful tool for studying drug intervention of surufatinib-related diarrhea.

Keywords: surufatinib, diarrhea, model, rat