重组人尿激酶原临床Ⅰ期药代动力学研究  

Clinical Phase Ⅰ Pharmacokinetics of rhproUK

作　　者：宋海晶[1] 杨伟志[2] 张卓梅[3] 欧伦[4] 陈方[4] 王清清[4] 董立厚[4] 刘秀文[4] 

机构地区：[1]解放军第306医院急诊部,北京100105 [2]同济大学附属上海市第十人民医院骨科,上海200072 [3]武警总医院妇产科,北京100039 [4]军事医学科学院放射与辐射医学研究所药理毒理研究室,北京100850

出　　处：《中国临床药理学与治疗学》2012年第6期672-676,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：国家"重大新药创制"科技重大专项;临床前药物代谢技术平台资助项目(2009ZX09304_004)

摘　　要：目的:研究健康受试者单次静脉注射重组人尿激酶原(rhproUK)后的药代动力性质。方法:采用ELISA分析方法测定血浆总uPA、sc-uPA抗原浓度以及联合免疫生色底物法测定纤溶活性变化。结果:健康受试者单次静脉注射给药剂量分别为20、40和60mg,血浆uPA、sc-uPA和纤溶活性的AUC和Cmax呈剂量依赖性增加,剂量比为1∶2∶3,AUCuPA之比为1∶2.1∶3.3;AUCsc-uPA之比1∶1.9∶2.9;不同给药剂量组间的uPA、sc-uPA抗原浓度的CLS、VSS、MRT、末端t1/2和tmax等参数无统计学差异。血浆纤溶活性浓度时间曲线的AUC和Cmax随剂量增加而增加,但表现出一定的非线性变化趋势,Cmax之比为1∶2.3∶3.9,AUC之比为1∶2.9∶4.7,CLS与Vd随剂量增加而逐渐减少。结论:健康受试者个体口服20～60mg剂量rhproUK后,血浆总u-PA、sc-uPA抗原浓度变化表现为线性药代动力学;而血浆纤溶活性浓度表现出非线性药代动力学特点。AIM： To investigate pharmacokinetics of rhproUK in healthy subjects. METH- ODS. ELISA and ELISA combined with chromogenic substrated method were used to deter- minate the plasma concentration of uPA, sc-uPA and plasminogen activity. RESULTS： The ratio of AUC of uPA and sc-uPA is 1 ： 2.1 ： 3.3 and 1 ： 1.9 ： 2.9 after single administration of rhproUK in the healthy subjects at the dose of 20, 40 and 60 mg per person,AUC and Cmax increase with dosage increasment, there are no significant difference in CLS, VSS, MRT, t1/2 and tmax b tween three groups. The increasment of AUC and Cmax in plasminogen activity are more than the increasment proportion of dosage, the ratio of Cmax and AUC is 1 ： 2.3 ： 3.9 and1 ： 2.9： 4.7, showed non-linear increasment. CLS and Vd reduce with dosage increasement. CONCLUSION： The course of u-PA, sc-uPA in healthy subjects fitted with the linear pharmacokinetics model in the range from 20 to 60 mg per person, But plasminogen activity showed slightly non linear pharmacokinetics.

关 键 词：人尿激酶原 药代动力学 酶联免疫吸附分析方法 血药浓度 

分 类 号：R972[医药卫生—药品]