Lindholm A, Jacobsen L V
Department of Clinical Pharmacology, Huddinge Hospital, Karolinska Institute, Stockholm, Sweden.
Clin Pharmacokinet. 2001;40(9):641-59. doi: 10.2165/00003088-200140090-00002.
Insulin aspart is a novel rapid-acting insulin analogue with improved subcutaneous absorption properties when compared with soluble human insulin. Pharmacokinetic studies show an absorption profile with a time to reach peak concentration (t(max)) about half that of human insulin, a peak plasma drug concentration (Cmax) approximately twice as high and shorter residence time. The potency and bioavailability of insulin aspart are similar to those of human insulin. The pharmacokinetics of insulin aspart have been studied in healthy Caucasian and Asian-Japanese volunteers, in patients with type 1 and 2 diabetes mellitus, and in children with diabetes, with both pre- and postprandial administration and during continuous subcutaneous insulin infusion (CSII). The pharmacokinetic profile was similar to that of another rapid-acting insulin analogue, insulin lispro, on the basis of published information for that agent. Pharmacodynamic studies show a smaller excursion of postprandial glucose with insulin aspart injected subcutaneously just before the meal compared with soluble human insulin injected 30 minutes before the meal in patients with type 1 diabetes mellitus, and an equivalent control in patients with type 2 diabetes displaying residual insulin production. In a treatment study, glucose excursions evaluated from 24-hour glucose profiles showed less variability with insulin aspart compared with human insulin. Adverse events, including hypoglycaemia-induced ventricular repolarisation and hypoglycaemic threshold and awareness, did not differ between insulin aspart and human insulin. The available data suggest that subcutaneous injections of insulin aspart just before meals better mimic the endogenous insulin profile in blood compared with human insulin, resulting in improved glucose control in a meal-related insulin regimen. This review summarises the clinical pharmacokinetics and pharmacodynamics of insulin aspart in relation to human insulin and insulin lispro.
门冬胰岛素是一种新型速效胰岛素类似物，与可溶性人胰岛素相比，其皮下吸收特性得到改善。药代动力学研究显示，其吸收曲线的达峰时间（t(max)）约为人胰岛素的一半，血浆药物峰浓度（Cmax）约高两倍，且驻留时间更短。门冬胰岛素的效价和生物利用度与人胰岛素相似。已在健康的白种人和亚洲日本志愿者、1型和2型糖尿病患者以及糖尿病儿童中研究了门冬胰岛素的药代动力学，包括餐前和餐后给药以及持续皮下胰岛素输注（CSII）期间。根据已发表的另一种速效胰岛素类似物赖脯胰岛素的信息，门冬胰岛素的药代动力学曲线与之相似。药效学研究表明，在1型糖尿病患者中，与餐前30分钟注射可溶性人胰岛素相比，餐前立即皮下注射门冬胰岛素后餐后血糖波动较小；在有残余胰岛素分泌的2型糖尿病患者中，两者的血糖控制效果相当。在一项治疗研究中，从24小时血糖谱评估的血糖波动显示，与使用人胰岛素相比，使用门冬胰岛素时的变异性更小。包括低血糖诱导的心室复极、低血糖阈值和低血糖意识在内的不良事件，门冬胰岛素与人胰岛素之间无差异。现有数据表明，与使用人胰岛素相比，餐前立即皮下注射门冬胰岛素能更好地模拟血液中的内源性胰岛素曲线，在与进餐相关的胰岛素治疗方案中能改善血糖控制。本综述总结了门冬胰岛素相对于人胰岛素和赖脯胰岛素的临床药代动力学和药效学。
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