Abstract
Objective: To assess the safety, feasibility and eluting efficiency of intrahepatic arterial delivery of sorafenib on normal liver tissue of rabbit. Methods: 24 New Zealand rabbits were randomly divided into three groups: group Ⅰ (Lipiodol-sorafenid), group Ⅱ (Lipiodol) and group Ⅲ (Sorafenib). Group Ⅰ and Ⅱ were treated by transcatheter selective hepatic arterial embolization with emulsions of lipiodol and sorafenib or with only lipiodol, while group Ⅲ was given hepatic arterial infusion with sorafenib. Sorafenib concentration in plasma was determined by HPLC (high performance liquid chromatography) in 0 min, 20 min, 1h, 2h, 4h, 8h, 16h, 32h and 48h respectively. The breathing rate, heart rate, rectal temperature and body weight were measured, as well the blood routine test and the function of liver, kidney, and heart. Two animals of each group were respectively killed in the 3rd day, 1st, 3rd and 6th week after treatment. Histopathologic study was done to liver, heart, kinney, lung, brain, gall bladder and intestine. Result: ① The peak sorafenib concentration (Cmax)and AUC(Area under curve) in plasma in groupⅠwas 2.46±0.101μg/ml and 945.72 ± 52.3 μg/mL.min respectively, while in group Ⅲ which was 3.78±0.180 ug/ml and 546.98±21.1μg/mL.min. Compared with groupⅢ, the Cmax and AUC of groupⅠhad a significant statistics difference (p<0.05). ② The breathing rate, heart rate, rectal temperature and AST/ALT,WBC,NEU% of group Ⅰand groupⅢhas a significant statistics difference(p<0.05) in the 3rd day. ③CK ,CK-MB, DB, Cr，BUN,RBC,PLT in plasma did not change in all group.④Local necrosis was seen in group Ⅰand group Ⅱin the 3rd day and 1st week, but they did not seem to be different. Group Ⅲ showed no necrosis. Granulation tissue with bile duty, portal vein and microfossils hyperplasia were seen in local necrosis area in the 3rd week. No pathological changes were found in brain, heart, kidney, intestine and gallbladder. Conclusion: TAE with emulsions of lipiodol and sorafenib is feasible, safe and has some slow-release effect.
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