摘要
目的:评价冻干重组胰高血糖素样肽-1受体激动剂在中国健康成年受试者中皮下单、多次给药的药代动力学特征。方法:研究纳入12名符合入选标准的健康成人受试者,男女各半。给药第1～8日,每日皮下注射5μg的rE-4一次,连续8日。结果:受试者第1日和第8日皮下注射rE-4后的药代动力学参数AUC0-t分别为690.2、718.0ng·h·L-1;AUC0-∞分别为779.8、797.9ng·h·L-1;tmax分别为0.89、0.79h;Cmax分别为201.4、212.7ng/L;t1/2Z分别为2.38、2.31h;CLz/F分别为6.7、6.5L/h。单、多次给药主要药代动力学参数差异无统计学意义,多次给药后累积指数为1.0017。试验期间无严重不良事件,仅发生1例轻度不良反应。结论:中国健康受试者每日1次连续8日皮下注射5μg rE-4安全性良好,药时曲线符合一室模型,体内无蓄积,可推荐进一步用于II期临床研究。
AIM： To study the pharmacokinetics of rE-4 （Lyophilized Recombinant Exendin-4） injection after single and multiple s. c. administration in Chinese healthy volunteers. METHODS： rE-4 injection was administrated s.c. to 6 male and 6 female Chinese adult healthy volunteers at the single dose of 5μg once a day for 8 days. RESULTS： After the administration of the 1st and the 8th day, the pharmaco- kinetic parameters AUC0-t was 690.2, 718.0 ng·h·L^-1 AUC0-∞ was 779.8, 797.9ng·h·L^-1 tmax was 0.89, 0.79 h, Cmax was 201.4, 212.7 ng·h·L^-1 t1/2z was 2.38, 2.31h; CLz/F was 6.7, 6.5 L/h, respectively. The AUC0-t,Cmax and t
1/2z of the single and multipleadministration were not statistically different and the accumulation index was 1. 0017. There were no serious adverse events observed but only one case of mild adverse reaction. CONCLUSION： The rE-4 was well tolerated in Chinese healthy volunteers. The concentration-time profiles of rE-4 were shown to fit the one-compartment model. No systemic accumulation appeared after the multiple-dose administration. Further phase II clinical trials towards rE-4 could be recommended.
出处
《中国临床药理学与治疗学》
CAS
CSCD
2012年第8期896-900,共5页
Chinese Journal of Clinical Pharmacology and Therapeutics
关键词
RE-4
药代动力学
安全性
中国健康受
rE-4
Pharmacokinetics
Safety
Chinese healthy volunteers
Subcutaneous administration
