摘要
目的：考察抗病毒蛋白I期临床试验受试者的2＇,5＇-寡聚腺苷酸合成酶水平,初步评价抗病毒蛋白乐复能的药效学特性。方法：采用2＇,5＇-寡腺苷酸（2-5A）放免检测试剂盒对I期临床试验血样进行分析,观察2＇,5＇-OAS水平。结果：10μg单次给药后2＇,5＇-OAS活性24-48 h达峰,至给药后120 h,除3#受试者外基本恢复至本底水平。10μg每日连续给药后血清2＇,5＇-OAS活性迅速升高,药后d 5变化趋势接近平台期,至第1次给药后25 d仍能维持在较高水平,至药后39 d,患者血清2＇,5＇-OAS活性值明显降低。10μg隔日连续给药组血清2＇,5＇-OAS活性变化趋势与每日连续给药组近似,但药后39 d尚能维持在较高水平。20μg隔日连续给药组连续7 d给予10μg乐复能后,血清2＇,5＇-OAS活性已升高至平台期,随后的20μg隔日连续给药将血清2＇,5＇-OAS活性值一直维持在较高的水平至连续给药结束。结论：2＇-5＇寡聚腺苷酸合成酶可以作为乐复能的临床疗效评价指标。
Objective： To investigate the level of 2＇,5＇-oligoadenylate synthetase（ 2＇,5＇-OAS） in the patients injected with a anti-virus protein,Lefuneng,in phase I clinical trial,and preliminarily evaluate pharmacodynamic properties of the anti-virus protein. Methods： The 2＇,5＇-oligoadenylate（ 2-5A） radioimmunoassay kit was used to determine the 2＇,5＇-OAS level in serum samples. Results： The activity of 2＇,5＇-OAS reached a peak in24 - 48 h after injecting a 10 μg single dose. At 120 h after administration,2＇,5＇-OAS activity in all the subjects returned to baseline except 3# subject. In the 10 μg qd group,2＇,5＇-OAS activity increased rapidly,on the fifth day reached a plateau after the first injection. The 2＇,5＇-OAS activity maintained at a high level in 25 days,whereas significantly reduced at 39 days after the first injection. The change trend of 2＇,5＇-OAS activity in the 10 μg qod group was similar to that of the 10μg qd group,while still maintained at a high level on the 39 th day. In the 20 μg qod group,the activity of 2＇,5＇-OAS was increased to a plateau after 10 μg qd administration for 7 days,and a high2＇,5＇-OAS level maintained until the end of the following 20 μg qod administration. Conclusion： 2＇,5＇-OAS can be used as the molecular index of pharmacodynamics of anti-virus protein.
出处
《中国新药杂志》
CAS
CSCD
北大核心
2014年第20期2437-2441,共5页
Chinese Journal of New Drugs
基金
国家"重大新药创制"科技重大专项(2011ZX09101-008-05)
