无针和有针注射器单次皮下注射重组生长激素注射液在中国成年健康受试者中的生物等效性预试验研究  

Pilot study investigating bioequivalence of single subcutaneous injections of recombinant growth hormone injection in Chinese adult healthy subjects using needle-free and needle-tipped syringes

作　　者：王松 王焱 陈霞 尹琳琳 WANG Song;WANG Yan;CHEN Xia;YIN Lin-lin(China National Clinical Research Center for Neurological Diseases,Beijing Tiantan Hospital,Capital Medical University,Beijing 100070,China)

机构地区：[1]首都医科大学附属北京天坛医院国家神经系统疾病临床医学研究中心,北京100070

出　　处：《中国临床药理学杂志》2022年第6期580-584,591,共6页The Chinese Journal of Clinical Pharmacology

基　　金：北京市自然科学基金面上基金资助项目(7212030)。

摘　　要：目的评价中国健康成人用快舒尔无针注射器(QS-P-01)和普通有针注射器单次皮下注射相同剂量重组生长激素(rhGH)注射液后的生物等效性。方法用单中心、随机、开放标签、单次给药、二周期交叉研究设计。8例健康受试者在2个研究周期注射生长抑素释放抑制激素或奥曲肽后分别通过2种注射器单次皮下注射rhGH 8 U。用酶联免疫吸附法测定血清生长激素(GH)浓度。用WinNonlin 8.1软件计算主要PK参数。结果用QS-P-01和普通有针注射器注射rhGH后,GH的主要药代动力学参数:C_(max)分别为(31.76±7.38)和(30.25±8.07)ng·mL^(-1),AUC_(0-t)分别为(219.56±37.75)和(205.68±38.15)ng·mL^(-1)·h,AUC_(0-∞)分别为(220.26±37.80)和(208.11±34.54)ng·mL^(-1)·h。相对于普通注射器,8例受试者血清GH的AUC_(0-∞)、AUC_(0-t)、C_(max)的几何均数比(GMR)的90%置信区间(CI)分别为105.70%(98.14%~113.84%),107.01%(99.61%~114.96%)和106.22%(89.30%~126.35%)。AUC_(0-∞)和AUC_(0-t)的90%CI均落入等效范围内,C_(max)的GMR在80.00%~125.00%,但90%CI略超出上限。非参数检验显示,2种注射器给药后的t_(max)差异无统计学意义(P>0.05)。结论无针注射器给药后血清GH的总体暴露参数AUC与普通注射器等效。Objective To evaluate the bioequivalence after a single subcutaneous injection of the same dose of recombinant growth hormone(rhGH)injection with a needle-free syringe(QS-P-01)and a common needle tipped syringe in healthy Chinese adults.Methods A randomized,open-label,single-dose,two-period,crossover study designing was adopted in the study.A total of 8 subjects received a single subcutaneous injection of rhGH 8 U via 2 syringes after injection of somatostatin or octreotide in 2 study cycles,respectively.The concentrations of serum growth hormone(GH)were measured by enzyme linked immunosorbent assay.The pharmacokinetic parameters were calculated by WinNonlin 8.1 program.Results The main pharmacokinetic parameters of GH after rhGH injection with QS-P-01 and needle syringe were as follows:C_(max) were(31.76±7.38)and(30.25±8.07)ng·mL^(-1),AUC_(0-t) were(219.56±37.75)and(205.68±38.15)ng·mL^(-1)·h,AUC_(0-∞)were(220.26±37.80)and(208.11±34.54)ng·mL^(-1)·h.The 90%confidence intervals(CI)for the geometric mean ratios(GMR)of AUC_(0-∞),AUC_(0-t),and C_(max) of GH in the 8 subjects were 105.70%(98.14%-113.84%),107.01%(99.61%-114.96%),and106.22%(89.30%-126.35%),respectively.The 90%CI of AUC_(0-∞)and AUC_(0-t) both fell into the equivalence range.The GMR of C_(max) was in 80.00%-125.00%,but the 90%CI was slightly beyond the upper limit.Nonparametric tests revealed that the difference in tm ax after administration via the 2 syringes did not reach statistical significance(P>0.05).Conclusion The overall exposure parameters(AUC)for serum GH after needle-free syringe administration was equivalent to needle-tipped syringes.

关 键 词：生物等效性 健康志愿者 药代动力学 重组人生长激素 

分 类 号：R977[医药卫生—药品]