Diabetes Centre for Children and Adolescents, Kinder- und Jugendkrankenhaus auf der Bult, Hannover, Germany.
Pediatr Diabetes. 2014 Feb;15(1):27-33. doi: 10.1111/pedi.12116.
Insulin degludec (IDeg) is a basal insulin with an ultra-long pharmacokinetic profile in adults that at steady-state produces remarkably flat and stable insulin levels; however, no studies have yet reported on the pharmacokinetic properties of IDeg in subjects younger than 18 years of age. This was a single-centre, randomised, single-dose, double-blind, two-period crossover trial conducted in children (6-11 years), adolescents (12-17 years), and adults (18-65 years) with type 1 diabetes. Subjects received a single subcutaneous dose of 0.4 U/kg IDeg or insulin glargine (IGlar), respectively, on two separate dosing visits, with pharmacokinetic blood sampling up to 72-h postdose. A total of 37 subjects (12 children, 13 adolescents, and 12 adults) completed the trial. Total exposure of IDeg after a single dose (AUCIDeg ,0-∞, SD ) was higher in children compared to adults [estimated ratio children/adults 1.48 (95% confidence interval, CI: 0.98; 2.24)] and in adolescents compared to adults [estimated ratio adolescents/adults 1.33 (95% CI: 1.08; 1.64)]; however, the difference was only statistically significant for the latter comparison. No statistically significant difference in maximum concentration of IDeg (Cmax, IDeg , SD ) was observed. Estimated ratios for Cmax, IDeg , SD were (children/adults) 1.20 (95% CI: 0.90; 1.60) and (adolescents/adults) 1.23 (95% CI: 1.00; 1.51). Simulated mean steady state pharmacokinetic profiles supported a flat and stable IDeg exposure across a 24-h dosing interval. IDeg was detectable in serum for at least 72 h (end of blood sampling period) in all subjects following single dose. In conclusion, the ultra-long pharmacokinetic properties of IDeg observed in adults are preserved in children and adolescents with type 1 diabetes.
德谷胰岛素（IDeg）是一种超长效基础胰岛素，在成年人中具有超长的药代动力学特征，在稳态下能显著地产生平稳且稳定的胰岛素水平；然而，目前尚无研究报道 IDeg 在 18 岁以下人群中的药代动力学特征。这是一项在儿童（6-11 岁）、青少年（12-17 岁）和成年（18-65 岁）1 型糖尿病患者中开展的单中心、随机、单剂量、双盲、两周期交叉试验。受试者分别接受了单次皮下注射 0.4U/kg IDeg 或甘精胰岛素（IGlar），在两次不同的给药访问中，给药后 72 小时内进行药代动力学血样采集。共有 37 名受试者（12 名儿童、13 名青少年和 12 名成年人）完成了试验。单次给药后 IDeg 的总暴露量（AUCIDeg,0-∞, SD ）在儿童中高于成年人[估计比值儿童/成年人 1.48（95%置信区间，CI：0.98；2.24）]，在青少年中高于成年人[估计比值青少年/成年人 1.33（95%CI：1.08；1.64）]；然而，只有后者的比较具有统计学意义。IDeg 的最大浓度（Cmax, IDeg, SD ）无统计学显著差异。Cmax, IDeg, SD 的估计比值为（儿童/成年人）1.20（95%CI：0.90；1.60）和（青少年/成年人）1.23（95%CI：1.00；1.51）。模拟的平均稳态药代动力学特征表明，在 24 小时给药间隔内，IDeg 的暴露量平稳且稳定。所有受试者在单次给药后至少 72 小时（血样采集结束时间）仍可检测到 IDeg 在血清中的存在。总之，在 1 型糖尿病儿童和青少年中，IDeg 的超长效药代动力学特征得到了保留。
