Abstract: 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 AUC_0-t was 690.2, 718.0 ng·h·L^-1; AUC_0-∞ was 779.8, 797.9 ng·h·L^-1; t_max was 0.89, 0.79 h, C_max was 201.4, 212.7 ng/L; t_1/2Z was 2.38, 2.31 h; CLz/F was 6.7, 6.5 L/h,respectively. The AUC_0-t,C_max and t_1/2z 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.

Key words: rE-4, Pharmacokinetics, Safety, Chinese healthy volunteers, Subcutaneous administration