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给药药代动力学研究

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。

Pharmacokinetics of rE-4 (Lyophilized Recombinant Exendin-4) in healthy volunteers after multiple subcutaneous injections

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 5 μg once a day for 8 days.RESULTS:After the administration of the 1st and the 8th day,the pharmacokinetic parameters AUC0-t was 690.2,718.0 ng·h·L-1;AUC0-∞ was 779.8,797.9 ng·h·L-1;tmax was 0.89,0.79 h,Cmax was 201.4,212.7 ng/L;t1/2Z was 2.38,2.31 h;CLz/F was 6.7,6.5 L/h,respectively.The AUC0-t,Cmax and t1/2z of the single and multiple administration 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.