注射用重组人成纤维细胞生长因子-21食蟹猴急性毒性试验研究

Acute toxicity of recombinant human fibroblast growth factor-21 injection in cynomolgus monkey

目的观察食蟹猴单次sc注射用重组人成纤维细胞生长因子-21(RH-FGF-21)的急性毒性反应。方法 8只健康食蟹猴,随机分成RH-FGF-21组和对照组,RH-FGF-21组6只,对照组2只,均雌雄各半,分别单次sc最大给药浓度和最大给药体积的供试品RH-FGF-21(9.0 mg/kg)和最大体积的对照品灭菌注射用水(1.0 m L/kg),给药后连续观察21 d。在给药前适应期和给药后观察期内进行动物的一般观察(外观、行为、饮食、反应能力、分泌物和排泄物等)、死亡情况、体质量变化、肛温、进食量、眼科和心电图检查、血液学和血液生化学检测、尿液观察和分析;观察期结束安乐死全部存活动物,进行组织病理学检查。结果动物体质量、肛温、进食量、心电图检查和眼科检查与同期对照组比较均未见明显异常;血液学检测、血液生化检测、尿液观察和分析结果、组织病理学检查也未见由药物引起的异常变化。结论在本试验条件下未发现由药物引起的急性毒性症状,9.0 mg/kg可认为是食蟹猴单次sc RH-FGF-21的最大给药量。

Objective The acute toxicity produced by single sc administration of recombinant human fibroblast growth factor-21（RH-FGF-21） in cynomolgus monkey. Method Eight healthy cynomolgus monkeys were randomly divided into the RH-FGF-21 group and the control group. There were six rats in the RH-FGF-21 group and two in the control group, male and female in half. Rats were treated with a single dose of RH-FGF-21（9.0 mg/kg） and sterile water（1.0 m L/kg） by sc administration, respectively. During the observation period（21 days）, general observations, body weight, local irritation, anus temperature, blood glucose, electrocardiogram（ECG）, and eyes were checked, and hematology, serum biochemistry, and urine were also detected. Also, all the surviving animals were euthanized at the end of the observation period for organic weights and histopathological examination. Results Compared to the control group, no obvious abnormality was found in general observations, food intake, body weight, anus temperature, ECG, and ophthalmologic examination in the RH-FGF-21 group. No obvious toxicity was observed in hematology, serum biochemistry, urine, and histopathological examination. Conclusion Under the experimental conditions, no serious toxicity of RH-FGF-21 was found. It is suggested that the maximum feasible dosage（MFD） for RH-FGF-21 was 9.0 mg/kg in cynomolgus monkey（single sc.）.