Steiner S, Hompesch M, Pohl R, Simms P, Flacke F, Mohr T, Pfützner A, Heinemann L
Biodel, Danbury, CT, USA.
Diabetologia. 2008 Sep;51(9):1602-6. doi: 10.1007/s00125-008-1095-8. Epub 2008 Jul 19.
AIMS/HYPOTHESIS: This study evaluates the pharmacodynamic and pharmacokinetic properties of the novel ultra-fast insulin product VIAject, a formulation of human soluble insulin and generally recognised as safe ingredients designed to increase the rate of absorption.
We performed five euglycaemic glucose clamps (Biostator; target blood glucose 5 mmol/l) in ten healthy volunteers. Using a crossover design with a fixed treatment order, 12 IU human soluble insulin, 12 U insulin lispro and 12 IU ultra-fast insulin were injected s.c. in the abdominal region on three study days. On the other two study days, 6 and 3 IU ultra-fast insulin were injected.
Subcutaneous injection of 12 IU ultra-fast insulin resulted in a time-action profile characterised by an even more rapid onset of action and maximal metabolic activity than insulin lispro: time to early half-maximal activity was 33 +/- 17 min (mean +/- SD) vs insulin lispro 51 +/- 13 min vs human soluble insulin 66 +/- 15 min (p < 0.05 ultra-fast insulin<insulin lispro<human soluble insulin); time to maximal activity was 136 +/- 56 min vs insulin lispro 152 +/- 30 min vs human soluble insulin 193 +/- 57 min (p < 0.05 ultra-fast insulin and insulin lispro<human soluble insulin). The metabolic activity in the first 2 h after injection was higher with ultra-fast insulin and insulin lispro than with human soluble insulin (AUC glucose infusion rate [GIR] 0-120 min: 915 +/- 301 and 781 +/- 174 vs 580 +/- 164 mg/kg; p < 0.05). A clear dose-response relationship was observed with the three doses of ultra-fast insulin: AUCGIR 0-120 min 12 IU 915 +/- 301 vs 6 IU 718 +/- 255 vs 3 IU 524 +/- 262 mg/kg (p < 0.05). The pharmacokinetic data confirmed the pharmacodynamic results.
CONCLUSIONS/INTERPRETATION: This study shows that the onset of action of VIAject is faster than that of human soluble insulin and insulin lispro.
目的/假设：本研究评估新型超快速胰岛素产品VIAject的药效学和药代动力学特性，该产品是一种人可溶性胰岛素制剂，含有普遍认为安全的成分，旨在提高吸收速率。
我们在10名健康志愿者中进行了5次正常血糖葡萄糖钳夹试验（Biostator；目标血糖5 mmol/L）。采用固定治疗顺序的交叉设计，在三个研究日于腹部皮下注射12 IU人可溶性胰岛素、12 U赖脯胰岛素和12 IU超快速胰岛素。在另外两个研究日，分别注射6 IU和3 IU超快速胰岛素。
皮下注射12 IU超快速胰岛素后的时间-作用曲线特征为起效比赖脯胰岛素更快、代谢活性更高：达到早期半最大活性的时间为33±17分钟（平均值±标准差），赖脯胰岛素为51±13分钟，人可溶性胰岛素为66±15分钟（超快速胰岛素<赖脯胰岛素<人可溶性胰岛素，p<0.05）；达到最大活性的时间为136±56分钟，赖脯胰岛素为152±30分钟，人可溶性胰岛素为193±57分钟（超快速胰岛素和赖脯胰岛素<人可溶性胰岛素，p<0.05）。注射后前2小时内，超快速胰岛素和赖脯胰岛素的代谢活性高于人可溶性胰岛素（葡萄糖输注速率曲线下面积[AUC GIR] 0 - 120分钟：915±301和781±174对比580±164 mg/kg；p<0.05）。观察到三种剂量超快速胰岛素之间有明确的剂量-反应关系：AUC GIR 0 - 120分钟，12 IU为915±301，6 IU为718±255，3 IU为524±262 mg/kg（p<0.05）。药代动力学数据证实了药效学结果。
结论/解读：本研究表明，VIAject的起效速度比人可溶性胰岛素和赖脯胰岛素更快。
