Mortensen H B, Lindholm A, Olsen B S, Hylleberg B
Paediatric Department, University Hospital 2600 Glostrup, Denmark.
Eur J Pediatr. 2000 Jul;159(7):483-8. doi: 10.1007/s004310051315.
The pharmacokinetics of the novel, rapid-acting insulin aspart were compared with those of soluble human insulin following subcutaneous administration in nine children (aged 6-12 years) and nine adolescents (aged 13-17 years) with stable type 1 diabetes. The study had a randomised, double-blind, two-period crossover design. Each patient received a single subcutaneous dose of insulin aspart or human insulin (0.15 IU/kg body weight) 5 min before breakfast and the plasma insulin and glucose concentrations were measured at intervals during the following 5 h. The pharmacokinetic profile of insulin aspart differed significantly from that of human insulin with a higher mean maximum serum insulin (Cmax ins), 881 +/- 321 (SD) pmol/l versus 422 +/- 193 pmol/l for human insulin (P < 0.001); and with a shorter median serum insulin tmax ins, 40.0 min (interquartile range: 40-50 min) versus 75.0 min (interquartile range: 60-120 min) for human insulin, (P < 0.001). An age-related effect on Cmax ins and area under the curve (AUC0-5 h ins) was observed with higher values in adolescents than in children for both insulin aspart and human insulin. Postprandial glycaemic control was improved with insulin aspart; the baseline-adjusted delta Cmax glu being lower for insulin aspart compared with human insulin (increase of 7.6 +/- 5.1 versus 9.4 +/- 4.4 mmol/l respectively, P < 0.05). The incidence of adverse events was similar for the two insulin types.
The more rapid onset of action of insulin aspart versus human insulin, previously observed in adults, is confirmed in a paediatric population with type 1 diabetes.
在9名患有稳定型1型糖尿病的儿童（6 - 12岁）和9名青少年（13 - 17岁）中，皮下注射新型速效胰岛素门冬胰岛素后，将其药代动力学与可溶性人胰岛素的药代动力学进行了比较。该研究采用随机、双盲、两期交叉设计。每位患者在早餐前5分钟接受单剂量皮下注射门冬胰岛素或人胰岛素（0.15 IU/kg体重），并在随后5小时内定期测量血浆胰岛素和葡萄糖浓度。门冬胰岛素的药代动力学特征与人类胰岛素显著不同，平均最大血清胰岛素（Cmax ins）更高，门冬胰岛素为881±321（标准差）pmol/L，人胰岛素为422±193 pmol/L（P<0.001）；血清胰岛素tmax ins中位数更短，门冬胰岛素为40.0分钟（四分位间距：40 - 50分钟），人胰岛素为75.0分钟（四分位间距：60 - 120分钟），（P<0.001）。观察到年龄对Cmax ins和曲线下面积（AUC0 - 5 h ins）有影响，门冬胰岛素和人胰岛素在青少年中的值均高于儿童。门冬胰岛素改善了餐后血糖控制；与人类胰岛素相比，门冬胰岛素的基线校正后ΔCmax glu更低（分别增加7.6±5.1与9.4±4.4 mmol/L，P<0.05）。两种胰岛素类型的不良事件发生率相似。
先前在成人中观察到的门冬胰岛素与人胰岛素相比起效更快的现象，在患有1型糖尿病的儿科人群中得到了证实。
