Søeborg Tue, Rasmussen Christian Hove, Mosekilde Erik, Colding-Jørgensen Morten
Danish Medicines Agency, Copenhagen, Denmark.
Eur J Pharm Sci. 2009 Jan 31;36(1):78-90. doi: 10.1016/j.ejps.2008.10.018. Epub 2008 Nov 5.
Many diabetic patients depend on regular and well-controlled administration of insulin to avoid unacceptable excursions in plasma glucose. A complicating factor is that the absorption of insulin shows a considerable variability, both between patients, and from administration to administration for the same patient. To understand the mechanisms that influence this variability we present a quantitative description of the absorption kinetics for both soluble insulin and insulin crystals. The concentration dependent distribution of insulin between different oligomers is first analysed and described. Next, the disappearance of soluble and crystalline insulin from subcutis is described and explained as a function of the administered dose, the insulin concentration and crystal specific parameters, but without diffusion. The effect of diffusion is then included, and the appearance of insulin in plasma following subcutaneous administration is simulated and discussed. Our results not only explain the observed variability, but they also explain how dose size, insulin concentration, insulin crystals etc. influence the absorption kinetics.
许多糖尿病患者依靠规律且控制良好的胰岛素给药来避免血糖出现不可接受的波动。一个复杂因素是，胰岛素的吸收在患者之间以及同一患者不同次给药之间都存在相当大的变异性。为了理解影响这种变异性的机制，我们对可溶性胰岛素和胰岛素晶体的吸收动力学进行了定量描述。首先分析并描述了胰岛素在不同寡聚体之间浓度依赖性分布。接下来，描述并解释了皮下组织中可溶性和结晶性胰岛素的消失情况，将其作为给药剂量、胰岛素浓度和晶体特定参数的函数，但不考虑扩散。然后纳入扩散的影响，并模拟和讨论皮下给药后胰岛素在血浆中的出现情况。我们的结果不仅解释了观察到的变异性，还解释了剂量大小、胰岛素浓度、胰岛素晶体等如何影响吸收动力学。
