【摘要】 目的 观察重组全人源抗新型冠状病毒单克隆抗体（2B11）注射液对恒河猴2周重复给药的毒性反应，确定无毒性反应的安全剂量及给药剂量、给药时间与毒性之间的关系，为临床用药提供参考。方法30只健康恒河猴，随机分成3组，每组10只，雌雄各半。溶媒对照组给予0.9%氯化钠注射液，实验组分别给予2B11 100和400 mg·kg^-1。每隔6 d iv给药1次，2周共给药3次，停药后恢复9周。实验期间进行一般症状观察、体重、摄食量、体温、眼科检查、血压、心电图、血常规、止凝血、血液生化及电解质、尿液、系统解剖、脏器系数、组织病理学和免疫学检测，同时进行抗药抗体（ADA）及血药浓度检测，并分析毒代动力学参数。结果 实验期间2B11 2个剂量组恒河猴一般症状、体重、摄食量、体温、眼科检查、血压、心电图、血常规、止凝血、血液生化及电解质、尿液、脏器系数、组织病理学和免疫学检测等指标均未见与受试物有关的明显改变。2B11 2个剂量组均未检测到ADA，血浆药物浓度变化基本一致，且与给药剂量呈正比，峰浓度之比和暴露量之比也与给药剂量呈正比，2B11注射液在体内基本呈线性动力学特征。结论 在本实验条件下，恒河猴2周重复iv给予2B11 3次是安全的，400 mg·kg^-1未观察到临床不良反应。更多还原

【Abstract】 OBJECTIVE To find out whether 2B11 will cause toxic reactions in animals, and determine the safe dose of without any toxic reactions and the relationship between the dose, time of administration and results of the toxicity test. METHODS Thirty healthy rhesus monkeys were selected and randomly divided into 3 groups, 10 in each group（half males and half females）, namely, the solvent control group, 2B11 100 and 400 mg·kg^-1 groups, respectively. The solvent control group was iv given0.9% sodium chloride injection, while the experimental groups were iv given 2B11 100 and 400 mg·kg^-1,respectively, once every 6 days, 3 times in 2 weeks, and allowed to recover for 9 weeks after drug withdrawal. During the test, the body weight, food intakes, body temperatures, ophthalmology, blood pressure, electrocardiograms, blood routine, anticoagulation, blood biochemistry, electrolytes, urine,systemic anatomy, organ weight and coefficient were observed, while histopathology and immunology tests were performed. At the same time, the anti-drug antibody（ADA） and plasma concentrations were determined, and toxikinetic parameters were analyzed. RESULTS During the experiment, the observation of general symptoms, body mass, food intakes, body temperatures, ophthalmology, blood pressure, electrocardiograms, blood routine, anticoagulation, blood biochemistry, electrolytes, urine, organ weight and coefficient, histopathology and immunology of animals in each dose group showed no significant changes related to the tested animals. ADA was not detected in any of the groups. Plasma drug concentrations in 2B11 100 and 400 mg·kg^-1 groups were basically consistent and proportional to the dose, so was the ratio of peak concentration and exposure. 2B11 injection showed linear kinetics in vivo.CONCLUSION Under the conditions set in this test, the 2-week repeated administration toxicity test of2B11 in rhesus monkeys is safe, and no clinical adverse reactions are observed at the dose level of400 mg·kg^-1, which provides reference for the follow-up clinical study of 2B11.更多还原