Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro
Pharmacokinetics and pharmacodynamics of subcutaneous injection of long-acting human insulin analog glargine, NPH insulin, and ultralente human insulin and continuous subcutaneous infusion of insulin lispro
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DOI：
10.2337/diabetes.49.12.2142
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发表时间：
2000-12-01
期刊：
影响因子：
7.7
通讯作者：
Bolli, GB
中科院分区：
文献类型：
--
作者：
Lepore, M;Pampanelli, S;Bolli, GB
为了比较长效甘精胰岛素类似物与NPH、ultralente和赖脯胰岛素连续皮下（SC）输注（连续皮下胰岛素输注[CSII]）的药代动力学/动力学，在异甘精胰岛素24小时钳夹期间对20例C肽阴性1型糖尿病患者进行了4次研究。患者接受0.3 U/kg甘精胰岛素或NPH胰岛素SC注射（随机序列，交叉设计）。在随后的两次情况下，他们接受ultralente（0.3 U/kg）或CSII（0.3 U.kg（-1. 24 h（-1））SC注射（随机序列，交叉设计）。SC胰岛素注射或CSII后，静脉（IV）胰岛素逐渐减量，输注葡萄糖以将血糖钳制在130 mg/dl，持续24 h。NPH（0.8 +/- 0.2 h）、CSII（0.5 +/- 0.1 h）和超长效胰岛素（1 +/- 0.2 h）与甘精胰岛素（1.5 +/- 0.3 h）相比，起效时间（定义为TV胰岛素减少>50%）更早（P < 0.05）（平均值+/- SE）。甘精胰岛素组的作用终止（定义为血糖升高>150 mg/dl）时间（22 +/- 4 h）晚于NPH组（14 +/- 3 h）（P < 0.05），但与超长效胰岛素组相似（20 +/- 6 h）。NPH和ultralente显示出峰浓度和作用（分别在4.5 +/- 0.5和10.1 +/- 1 h），随后逐渐减弱，而甘精胰岛素没有峰，但具有类似CSII的平坦浓度/作用曲线。甘精胰岛素的个体间变异性（计算为不同治疗中血浆胰岛素浓度和葡萄糖输注速率的SD差异）低于NPH和ultralente（P < 0.05），但与甘精胰岛素和CSII（NS）相似。总之，NPH和ultralente都是峰值胰岛素。超慢的作用持续时间更长，但受试者间变异性也大于NPH。甘精胰岛素是一种无峰值胰岛素，持续时间近24小时，受试者间变异性低于NPH和ultralente，与基础胰岛素替代的金标准CSII非常相似。
To compare the pharmacokinetics/dynamics of the long-acting insulin analog glargine with NPH, ultralente, and continuous subcutaneous (SC) infusion of insulin lispro (continuous subcutaneous insulin infusion [CSII]), 20 C-peptide-negative type 1 diabetic patients mere studied on four occasions during an isoglycemic 24-h clamp. Patients received SC injection of either 0.3 U/kg glargine or NPH insulin (random sequence, crossover design). On two subsequent occasions, they received either an SC injection of ultralente (0.3 U/kg) or CSII (0.3 U.kg(-1).24 h(-1)) (random sequence, crossover design). After SC insulin injection or CSII, intravenous (IV) insulin was tapered, and glucose was infused to clamp plasma glucose at 130 mg/dl for 24 h. Onset of action (defined as reduction of TV insulin >50%) was earlier with NPH (0.8 +/- 0.2 h), CSII (0.5 +/- 0.1 h), and ultralente (1 +/- 0.2 h) versus glargine (1,5 +/- 0.3 h) (P < 0.05) (mean +/- SE). End of action (defined as an increase in plasma glucose >150 mg/dl) occurred later with glargine (22 +/- 4 h) than with NPH (14 +/- 3 h) (P < 0.05) but was similar with ultralente (20 +/- 6 h). NPH and ultralente exhibited a peak concentration and action (at 4.5 +/- 0.5 and 10.1 +/- 1 h, respectively) followed by waning, whereas glargine had no peak but had a fiat concentration/action profile mimicking CSII. Interindividual variability (calculated as differences in SD of plasma insulin concentrations and glucose infusion rates in different treatments) was lower with glargine than with NPH and ultralente (P < 0.05) but was similar with glargine and CSII (NS). In conclusion, NPH and ultralente are both peak insulins. Duration of action of ultralente is greater, but intersubject variability is also greater than that of NPH. Glargine is a peakless insulin, it lasts nearly 24 h, it has lower intersubject variability than NPH and ultralente, and it closely mimics CSII, the gold standard of basal insulin replacement.