【摘要】 目的采用正常血糖-高胰岛素钳夹技术评估短效重组人胰岛素在健康人体内的药动学及药效学。方法采用单中心、随机、双肓、平行交叉研究,22名健康志愿者在正常血糖—高胰岛素钳夹平台基础上,分别前后接受皮下注射短效重组人胰岛素和优泌林R两次10 h钳夹试验,于给药前120、90、60、30 min及给药后0、10、20、30、40、50、60、70、80、90、100、110、120、150、180、210、240、270、300、330、360、390、420、450、480 min取血测定血清胰岛素水平,同时计算给药后的前2 h每10 min的葡萄糖输注速率和后6 h的每15 min的葡萄糖输注速率(GIR),计算药动学和药效学参数。结果 20名志愿者纳入分析,平均25.8±1.76岁,体重指数21.52±1.21 kg.m-1。受试制剂和参比制剂在钳夹基线稳态期组间的葡萄糖GIR和C肽抑制率接近,差异无统计学意义。短效重组人胰岛素和优泌林R皮下给药后有关药动学参数如下:胰岛素的Cmax分别为108.64±18.98、111.92±118.02 mU.L-1;Tmax分别为78.00±31.56、86.00±38.44 min;AUC0～480分别为20.6801±5.5153、21.3471±5.4641 U.L-1,葡萄糖GIRmax分别为5.55±1.73、6.16±1.69 mg.kg-1.min-1,结果表明:短效重组人胰岛素和优泌林R之间的药动学参数差异无统计学意义。结论正常血糖-高胰岛素钳夹技术可准确评估胰岛素制剂的药动学和药效学。两种制剂的药动学参数无显著差异,具生物等效性。更多还原

【Abstract】 OBJECTIVE To evaluate the pharmacokinetics(PK) and pharmacodynamics of subcutaneous injection of rh-insulin by euglycemic clamp technique in healthy volunteers.METHODS This was a mono-centre,randomized,double blinded two periods,cross-over open-label comparative study in 22 healthy volunteers,who were randomly received the rh-insulin or regular insulin subcutaneous administration.All subjects underwent an oral glucose tolerance test,an evaluation of their metabolic profiles and a 10 h euglycaemic hyperinsulinaemic clamp test.The blood samples of the clamp study at-120,-90,-60,-30,0,10,20,30,40,50,60,70,80,90,100,110,120,150,180,210,240,270,300,330,360,390,420,450,480 min were taken for insulin detection,meanwhile,glucose infusion rate(GIR) were determined per 10 min over the first 2 h and per 15 min over the next period of 6 h.RESULTS During the euglycaemic hyperinsulinaemic clamp,whole-body glucose use and C-peptide suppression were similar in the two treatment groups at baseline,and the Cmax of insulin were of tested and reference preparation were 108.64±18.98,111.92±118.02 mU·L-1,Tmax were 78.00±31.56,86.00±38.44 min,AUC0～480 were 20.6801±5.5153,21.3471±5.4641 U·L-1,GIRmax were 5.55±1.73,6.16±1.69 mg·kg-1·min-1,respectively.CONCLUSION Euglycemic-hyperinsulinemic clamp technique is use for the research of insulin pharmacotinetics and pharmacodynamics.The study shows that there were no significant differences of the pharmacokinetic and pharmacodynamic properties between the rh-insulin and regular insulin,the tested rh-insulin and reference preparation are bioequivalent.更多还原