重组抗人血小板GPIIbIIIa嵌合单抗F(ab27)2.docVIP

重组抗人血小板GPIIb/IIIa嵌合单抗F(ab’)2 在Beagle犬体内的药代动力学 李佐刚a ，闻镍a ，季顺东b ，汤瑶a ，孙旭a ，于敏a，王秀文a，王军志a，李波a（a.中国药品生物制品检定所 国家药物安全评价监测中心，北京亦庄100176；b.苏州大学） 摘要: 目的 本文研究了重组抗人血小板GPIIb/IIIa嵌合单抗F(ab’)2经静脉单次给药后在Beagle犬中的药代动力学。方法 按不同时间点采血分离血采用双抗体夹心酶联免疫吸附实验（）法测定血中的浓度进行曲线拟合并计算参数。结果·kg-1)后为±0.65) h、(8.28±0.68) h和(7.03±3.26) h，CLs与Vss随着剂量的减小发生增加的变化，血药浓度-时间曲线下面积AUC分别为2453.70 ±371.59、1097.64±142.11和362.63±169.12 ·h·ng·mL-1，剂量之比为3:2:1，对应的AUC比值为6.8:3:1, 剂量与AUC成正相关性，相关系数R2=0.9714，但是AUC的增加量大于剂量的增加量。 结论血浆浓度。GPIIb/IIIa mAb [ chimeric F(ab’)2 ] following intravenous administration in Beagle dogs Li Zuo-ganga, Wen Niea，Ji Shun-dongb，Tang Yaoa，Sun Xuna ，Yu Mina ，Wang Jun-zhia，Wang Xiu-wena，Li Boa（a:National Center for Safety Evaluation of Drugs, National Institute for the Control of Pharmaceutical and Biological Products, Beijing 100176, b: Suzhou University） ABSTRACT: OBJECTIVE To evaluate the pharmacokinetics of mouse-human chimeric F(ab’)2 fragment in Beagle dogs. METHODS 12 health Beagle dogs were divided into three groups randomly (2 male and 2 female in each group), and were administrated a single intravenous dosages of 1.2, 0.8, 0.4 mg·kg-1 of chimeric F(ab’)2 respectively, chimeric F(ab’)2 in plasma of 12 Beagle dogs at different sampling time was determined by ELISA. The pharmacokinetic parameters were estimated by WinNonlin software and compared by SPSS statistic analysis. RESULTS The mean concentration-time curves of chimeric F(ab’)2 was fitted to noncompartment modul. The main pharmacokinetic parameters as follows: T1/2(7.35±0.65) h、(8.28±0.68) h and (7.03±3.26) h, AUCinf (2453.70 ±371.59)、(1097.64±142.11) and (362.63±169.12) ·h·ng·mL-1，respectively. With the decrease of dosage, CLs and Vss were increased. CONCLUSION AUCinf are dose-dependent pharmacokinetics but not dose-proportinal over the dose range o.4 -1.2mg·kg-1. There is no significant difference in the pharmacokinetics parameters between male and female dogs. KEY WORDS: ELISA; Thrombocytopenia; Anti-GPIIb/IIIa; chimeric F(ab’)2 f