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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。
OBJECTIVE: To evaluate the pharmacokinetic profiles of lyophilized recombinant glucagon-like peptide-1 receptor agonists in single and multiple subcutaneous in Chinese healthy adult subjects. METHODS: The study included 12 healthy adult subjects who met the inclusion criteria, half-men and half-men. On the 1st to the 8th day of administration, 5 μg of rE-4 was injected subcutaneously once daily for 8 consecutive days. Results: The pharmacokinetic parameters AUC0-t were 690.2 and 718.0 ng · h · L-1 after subcutaneous injection of rE-4 on day 1 and day 8, respectively. The AUC0-∞ were 779.8 and 797.9 ng · h · L-1; tmax were 0.89,0.79h; Cmax were 201.4,212.7ng / L; t1 / 2Z were 2.38,2.31h; CLz / F were 6.7,6.5L / h. The main pharmacokinetic parameters of single and multiple administrations showed no significant difference. The cumulative index after multiple administrations was 1.0017. No serious adverse events during the trial, only one case of mild adverse reactions. CONCLUSIONS: Chinese healthy volunteers are safe once a day on the 8th for 5 consecutive days with 5μg rE-4 subcutaneously. The curve of the drug is consistent with a one-compartment model. There is no accumulation in the body and it can be recommended for further study in phase II.