目的 觀察食蟹猴單次sc注射用重組人成纖維細(xì)胞生長因子-21（RH-FGF-21）的急性毒性反應(yīng)。方法 8只健康食蟹猴，隨機(jī)分成RH-FGF-21組和對照組，RH-FGF-21組6只，對照組2只，均雌雄各半，分別單次sc最大給藥濃度和最大給藥體積的供試品RH-FGF-21（9.0 mg/kg）和最大體積的對照品滅菌注射用水（1.0 mL/kg），給藥后連續(xù)觀察21 d。在給藥前適應(yīng)期和給藥后觀察期內(nèi)進(jìn)行動物的一般觀察（外觀、行為、飲食、反應(yīng)能力、分泌物和排泄物等）、死亡情況、體質(zhì)量變化、肛溫、進(jìn)食量、眼科和心電圖檢查、血液學(xué)和血液生化學(xué)檢測、尿液觀察和分析；觀察期結(jié)束安樂死全部存活動物，進(jìn)行組織病理學(xué)檢查。結(jié)果 動物體質(zhì)量、肛溫、進(jìn)食量、心電圖檢查和眼科檢查與同期對照組比較均未見明顯異常；血液學(xué)檢測、血液生化檢測、尿液觀察和分析結(jié)果、組織病理學(xué)檢查也未見由藥物引起的異常變化。結(jié)論 在本試驗條件下未發(fā)現(xiàn)由藥物引起的急性毒性癥狀，9.0 mg/kg可認(rèn)為是食蟹猴單次sc RH-FGF-21的最大給藥量。

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 mL/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.).

國家科技重大新藥創(chuàng)制項目（2015ZX09501004）