Vora J P, Owens D R, Dolben J, Atiea J A, Dean J D, Kang S, Burch A, Brange J
Department of Medicine, University of Wales College of Medicine, Health Park, Cardiff.
BMJ. 1988 Nov 12;297(6658):1236-9. doi: 10.1136/bmj.297.6658.1236.
To compare the rate of absorption from subcutaneous tissue and the resulting hypoglycaemic effect of iodine-125 labelled soluble human insulin and a monomeric insulin analogue derived by recombinant DNA technology.
Single blind randomised comparison of equimolar doses of 125I labelled soluble human insulin and insulin analogue.
Study in normal people at a diabetes research unit and a university department of medical physics.
Seven healthy male volunteers aged 20-39 not receiving any other drugs.
After an overnight fast and a basal period of one hour two doses (0.05 and 0.1 U/kg) of 125I labelled soluble human insulin and insulin analogue were injected subcutaneously into the anterior abdominal wall on four separate days.
To find a fast acting insulin for meal related requirements in insulin dependent diabetics. MEASUREMENTS and main results--Residual radioactivity at the injection site was measured continuously for the first two hours after injection of the 125I labelled preparations and thereafter for five minutes simultaneously with blood sampling. Frequent venous blood samples were obtained over six hours for determination of plasma immunoreactive insulin, insulin analogue, glucose, and glucagon values. Time to 50% of initial radioactivity at the injection site for the insulin analogue compared with soluble insulin was 61 v 135 minutes (p less than 0.05) with 0.05 U/kg and 67 v 145 minutes (p less than 0.001) with 0.1 U/kg. Concentrations in plasma increased faster after the insulin analogue compared with soluble insulin, resulting in higher plasma concentrations between 10 and 150 minutes (0.001 less than p less than 0.05) after 0.05 U/kg and between 40 and 360 minutes (0.001 less than p less than 0.05) after 0.1 U/kg. The hypoglycaemic response to insulin analogue was a plasma glucose nadir at 60 minutes with both doses compared with 90 and 120 minutes with soluble insulin at 0.5 and 0.1 U/kg respectively. The response of glucagon substantiated the earlier and more dramatic hypoglycaemic effect with the insulin analogue.
The much faster absorption from subcutaneous tissue of the disubstituted monomeric insulin analogue compared with soluble insulin suggests that the analogue may be a potential candidate for rapid insulin delivery after subcutaneous bolus injection.
比较皮下组织对碘 - 125标记的可溶性人胰岛素和通过重组DNA技术衍生的单体胰岛素类似物的吸收速率及其产生的降血糖效果。
等摩尔剂量的125I标记的可溶性人胰岛素和胰岛素类似物的单盲随机对照试验。
在糖尿病研究单位和大学医学物理部门对正常人进行研究。
7名年龄在20 - 39岁之间、未服用任何其他药物的健康男性志愿者。
在过夜禁食和1小时基础期后，在4个不同日期将两剂（0.05和0.1 U/kg）125I标记的可溶性人胰岛素和胰岛素类似物皮下注射到前腹壁。
为胰岛素依赖型糖尿病患者寻找一种用于满足与进餐相关需求的速效胰岛素。测量和主要结果 - 在注射125I标记制剂后的前两小时连续测量注射部位的残留放射性，此后每5分钟测量一次并同时采集血样。在6小时内频繁采集静脉血样，以测定血浆免疫反应性胰岛素、胰岛素类似物、葡萄糖和胰高血糖素值。胰岛素类似物与可溶性胰岛素相比，注射部位放射性降至初始值50%的时间，0.05 U/kg剂量时为61对135分钟（p < 0.05），0.1 U/kg剂量时为67对145分钟（p < 0.001）。与可溶性胰岛素相比，胰岛素类似物注射后血浆浓度升高更快，在0.05 U/kg剂量后10至150分钟（0.001 < p < 0.05）以及0.1 U/kg剂量后40至360分钟（0.001 < p < 0.05）时血浆浓度更高。两种剂量的胰岛素类似物降血糖反应的血糖最低点在60分钟，而可溶性胰岛素在0.5和0.1 U/kg剂量时分别为90分钟和120分钟。胰高血糖素的反应证实了胰岛素类似物更早且更显著的降血糖作用。
与可溶性胰岛素相比，二取代单体胰岛素类似物从皮下组织的吸收速度快得多，这表明该类似物可能是皮下推注注射后快速胰岛素递送的潜在候选药物。
