Pharmacokinetics and pharmacodynamics of insulin aspart in patients with Type 2 diabetes : Assessment using a meal tolerance test under clinical conditions
Pharmacokinetics and pharmacodynamics of insulin aspart in patients with Type 2 diabetes : Assessment using a meal tolerance test under clinical conditions
复制标题
门冬胰岛素在 2 型糖尿病患者中的药代动力学和药效学：在临床条件下使用膳食耐受试验进行评估
DOI：
10.1111/j.1440-1681.2012.05708.x
复制
发表时间：
2012
期刊：
影响因子：
--
通讯作者：
T Takamura
中科院分区：
文献类型：
--
作者：
H Ando;S Kurita;A Shimizu;K Kato;K Ishikura;K Taji;M Uno;Y Takeshita;H Misu;A Fujimura;S Kaneko;T Takamura
很少有研究评估速效胰岛素类似物在2型糖尿病患者中的药代动力学，特别是在临床条件下。本研究的目的是评估单独使用类似物治疗的2型糖尿病患者的胰岛素天冬氨酸的药代动力学和药效学。在一项随机交叉研究中，对20名患者进行了自行注射常规剂量（0.05-0.22 U/kg）的胰岛素分离和不注射胰岛素分离的饮食耐受性试验。天冬氨酸胰岛素剂量（每体重）与最大浓度（r2= 0.59， P< 0.01）、天冬氨酸胰岛素浓度-时间曲线下面积（r2= 0.53， P< 0.01）呈极显著相关。然而，达到最大浓度的时间（Tmax）从< 60到≥120 min变化很大，与剂量（r2= 0.02；P= 0.51）或体重指数（r2= 0.02；P= 0.57）无关。注射天冬氨酸胰岛素加重餐后迟发性高胰岛素血症，主要发生在tmax≥120 min的患者。在药效学方面，天冬氨酸胰岛素对餐后高血糖、高胰高血糖素血症和高脂血症有良好的作用。这种胰岛素类似物的tmax在个体之间差异很大，tmax值较高的患者尤其加剧了延迟性高胰岛素血症。确定导致个体间吸收滞后时间差异的因素对于提高胰岛素分离的有效性和安全性至关重要。
Few studies have evaluated the pharmacokinetics of rapid‐acting insulin analogues in patients with Type 2 diabetes, especially under clinical conditions. The aim of the present study was to assess both the pharmacokinetics and pharmacodynamics of insulin aspart in Type 2 diabetic patients who were being treated with the analogue alone.Meal tolerance tests with and without self‐injection of a customary dose of insulin aspart (0.05–0.22 U/kg) were conducted in 20 patients in a randomized cross‐over study.The dose of insulin aspart (per bodyweight) was significantly correlated with both the maximum concentration (r2= 0.59;P< 0.01) and area under the concentration–time curve for insulin aspart (r2= 0.53;P< 0.01). However, the time to maximum concentration (Tmax), which varied widely from < 60 to ≥ 120 min, was not associated with either dosage (r2= 0.02;P= 0.51) or body mass index (r2= 0.02;P= 0.57). Injection of insulin aspart exacerbated delayed hyperinsulinaemia after meal loading, mainly in patients withTmax≥ 120 min. With regard to pharmacodynamics, insulin aspart had favourable effects on postprandial hyperglycaemia, hyperglucagonaemia and hyperlipidaemia.TheTmaxfor this insulin analogue differed greatly between individuals and delayed hyperinsulinaemia was particularly exacerbated in patients with higherTmaxvalues. Identification of the factors contributing to interindividual variation in the absorption lag time is essential for improving the efficacy and safety of insulin aspart.