Bott S, Tusek C, Jacobsen L V, Endahl L, Draeger E, Kapitza C, Heise T
Profil Institut für Stoffwechselforschung GmbH, Neuss, Germany.
Diabet Med. 2006 May;23(5):522-8. doi: 10.1111/j.1464-5491.2006.01839.x.
This study investigated the pharmacodynamic and pharmacokinetic characteristics of the novel long-acting insulin analogue insulin detemir (IDet) under single-dose and steady-state conditions in comparison with those of NPH insulin at steady state.
Twenty-five subjects with Type 1 diabetes [seven females, 18 males, mean age (+/- sd) 39 +/- 12 years, body mass index 24 +/- 3 kg/m(2)] participated in three 24-h glucose clamps. IDet or NPH were given at 12-h intervals in fixed, individualized doses. The first clamp assessed the metabolic effect of NPH at steady state, the second investigated the effect of two single injections of IDet. Subjects continued IDet treatment for 7-14 days, after which the third clamp was performed to investigate IDet at steady state.
At steady state, the metabolic effect of IDet was constant over 24 h while a clear peak in the metabolic effect [expressed as glucose infusion rates (GIR)] was observed with NPH after each injection. The fluctuation in the metabolic effect (maximum GIR divided by the average of the GIR values at the interval ends) was significantly lower in the second 12 h of the experiments with IDet under steady-state conditions compared with NPH (fluctuation(12-24 h) 1.27 +/- 0.17 vs. 1.56 +/- 0.72, P < 0.05). The overall metabolic effect of IDet at steady state was comparable with that of NPH [GIR-area under curve (AUC)(0-24 h): 5697 +/- 1861 vs. 5929 +/- 1965 mg/kg] whereas a significantly lower effect (5187 +/- 1784 mg/kg, P = 0.01 vs. steady state) was observed following the first two IDet injections. GIR values at the end of clamp day 2 (first doses) and clamp day 3 (steady state) were comparable [GIR(trough 24 h) 3.7 +/- 1.7 vs. 3.8 +/- 1.6 mg/(kg x min) NS], indicating that IDet had reached steady state after the first two injections.
IDet administered twice daily reached steady state after the second injection and showed a constant metabolic effect over time under steady-state conditions. This should facilitate basal insulin substitution and decrease the risk of hypoglycaemia in insulin-treated subjects.
本研究调查了新型长效胰岛素类似物地特胰岛素（IDet）在单剂量和稳态条件下的药效学和药代动力学特征，并与中性鱼精蛋白锌胰岛素（NPH胰岛素）的稳态特征进行比较。
25名1型糖尿病患者[7名女性，18名男性，平均年龄（±标准差）39±12岁，体重指数24±3kg/m²]参与了三次24小时葡萄糖钳夹试验。以固定的个体化剂量每隔12小时给予IDet或NPH。第一次钳夹评估NPH在稳态时的代谢作用，第二次研究两次单次注射IDet的作用。受试者持续接受IDet治疗7 - 14天，之后进行第三次钳夹以研究IDet在稳态时的情况。
在稳态时，IDet的代谢作用在24小时内保持恒定，而每次注射NPH后，其代谢作用[以葡萄糖输注速率（GIR）表示]出现明显峰值。在稳态条件下，与NPH相比，IDet实验的第二个12小时内代谢作用的波动（最大GIR除以该时间段末端GIR值的平均值）显著更低（波动（12 - 24小时）1.27±0.17对1.56±0.72，P < 0.05）。IDet在稳态时的总体代谢作用与NPH相当[GIR - 曲线下面积（AUC）（0 - 24小时）：5697±1861对5929±1965mg/kg]，而在前两次注射IDet后观察到作用显著更低（5187±l784mg/kg，与稳态相比P = 0.01）。钳夹第2天（首次给药）和钳夹第3天（稳态）结束时的GIR值相当[GIR（24小时谷值）3.7±1.7对3.8±1.6mg/（kg·min），无显著性差异]，表明在前两次注射后IDet已达到稳态。
每日两次给药的IDet在第二次注射后达到稳态，且在稳态条件下随时间显示出恒定的代谢作用。这应有助于基础胰岛素替代，并降低胰岛素治疗患者低血糖的风险。
