Owens D R, Coates P A, Luzio S D, Tinbergen J P, Kurzhals R
University of Wales College of Medicine, Diabetes Research Unit, Academic Centre, Llandough Hospital, Penarth, South Glamorgan, UK.
Diabetes Care. 2000 Jun;23(6):813-9. doi: 10.2337/diacare.23.6.813.
To determine the subcutaneous absorption rates and the appearance in plasma of 3 formulations of the long-acting human insulin analog insulin glargine (HOE 901) differing only in zinc content (15, 30, and 80 microg/ml).
We conducted 2 studies. Study 1 compared the subcutaneous abdominal injection of 0.15 U/kg of 125I-labeled insulin glargine[15], insulin glargine[80], NPH insulin, and placebo. In study 2, 0.2 U/kg of insulin glargine[30] was injected into the arm, leg, and abdominal regions. Both studies had a randomized crossover design; each enrolled 12 healthy men, aged 18-50 years.
In study 1, the time in hours for 25% of the administered radioactivity to disappear after bolus subcutaneous injection (T75%) for NPH insulin indicated a significantly faster absorption rate compared with the 2 insulin glargine formulations (3.2 vs. 8.8 and 11.0 h, respectively P < 0.0001). Mean residual radioactivity with NPH insulin was also significantly lower at 24 h (21.9 vs. 43.8 and 52.2%, P < 0.0001). The calculated plasma exogenous insulin concentrations after NPH insulin were substantially higher than those with insulin glargine, reaching a peak within the first 6 h after administration before declining. Insulin glargine, however, did not exhibit a distinct peak. Weighted average plasma glucose concentration between 0 and 6 h was significantly lower after NPH compared with insulin glargine (P < 0.001). In study 2, there were no significant differences in the absorption characteristics of insulin glargine between the 3 injection sites (T75% = 11.9, 15.3, and 13.2 h for arm, leg, and abdomen, respectively) or in residual radioactivity at 24 h.
Subcutaneous absorption of insulin glargine is delayed compared with NPH insulin. There is little or no difference in the absorption rate of insulin glargine between the main subcutaneous injection sites.
测定仅锌含量不同（15、30和80微克/毫升）的3种长效人胰岛素类似物甘精胰岛素（HOE 901）制剂的皮下吸收率及血浆中的表现。
我们进行了2项研究。研究1比较了皮下腹部注射0.15 U/千克的125I标记的甘精胰岛素[15]、甘精胰岛素[80]、中性精蛋白锌胰岛素（NPH胰岛素）和安慰剂。在研究2中，将0.2 U/千克的甘精胰岛素[30]注射到手臂、腿部和腹部区域。两项研究均采用随机交叉设计；每项研究招募了12名年龄在18至50岁之间的健康男性。
在研究1中，NPH胰岛素单次皮下注射后25%的给药放射性消失所需的时间（T75%）以小时计，表明其吸收率明显快于两种甘精胰岛素制剂（分别为3.2小时对8.8小时和11.0小时，P<0.0001）。NPH胰岛素在24小时时的平均残留放射性也显著更低（21.9%对43.8%和52.2%，P<0.0001）。NPH胰岛素给药后计算出的血浆外源性胰岛素浓度显著高于甘精胰岛素，在给药后的前6小时内达到峰值然后下降。然而，甘精胰岛素未显示出明显的峰值。与甘精胰岛素相比，NPH胰岛素给药后0至6小时的加权平均血浆葡萄糖浓度显著更低（P<0.001）。在研究2中，3个注射部位之间甘精胰岛素的吸收特征（手臂、腿部和腹部的T75%分别为11.9小时、15.3小时和13.2小时）或24小时时的残留放射性均无显著差异。
与NPH胰岛素相比，甘精胰岛素的皮下吸收延迟。主要皮下注射部位之间甘精胰岛素的吸收率几乎没有差异或无差异。
