ter Braak E W, Woodworth J R, Bianchi R, Cerimele B, Erkelens D W, Thijssen J H, Kurtz D
Lilly Laboratory for Clinical Research, Eli Lilly and Company, Wishard Memorial Hospital, Indianapolis, IN 46219, USA.
Diabetes Care. 1996 Dec;19(12):1437-40. doi: 10.2337/diacare.19.12.1437.
The pharmacokinetics and glucodynamics of a new insulin analog, insulin lispro, and regular human insulin were compared and contrasted after subcutaneous administrations in femoral, deltoid, and abdominal injection sites.
Single 0.2 U/kg doses of insulin lispro and regular insulin were administered to 12 healthy subjects in a six-way randomized crossover fashion. Each dose was given after an overnight fast in one of three injection sites: abdominal, deltoid, or femoral. Study drugs were given during a manual euglycemic glucose clamp. Blood samples were collected over the 12-h clamp for measurement of insulin-reactive components, with pharmacokinetic and glucodynamic measurements derived from these serum insulin and clamp measurements.
Glucodynamic comparisons between insulin lispro and regular insulin showed a greater maximum infusion rate (Rmax) at an earlier time (TRmax), regardless of injection site. The total glucose infused (Gtot) showed nearly identical values between sites for insulin lispro. Regular insulin showed greater Gtot values from deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater Gtot, primarily driven by the increased Gtot from deltoid and femoral injections. Greater maximum serum insulin concentrations (Cmax) were experienced with insulin lispro at earlier times (tmax), regardless of the injection site (P < 0.001). Abdominal administrations produced the greatest Cmax values at the earliest tmax for both regular insulin and insulin lispro. Deltoid and femoral injections had lower Cmax values for both compounds. Shifts also occurred with tmax, although these shifts were much greater with regular insulin than with insulin lispro. Equivalent area under the curve (AUC) values were found when compared between compounds.
Slower absorption from deltoid and femoral administrations resulted in an increased duration of action for both regular insulin and insulin lispro when compared to abdominal administration. However, notable increases in the onset of action were only apparent with regular insulin. The consistency with insulin lispro response from abdominal and extremity injection sites allows more potential sites for subcutaneous injection with an assured rapid response.
比较新型胰岛素类似物赖脯胰岛素与常规人胰岛素在股部、三角肌和腹部注射部位皮下给药后的药代动力学和糖动力学。
以六向随机交叉方式，给12名健康受试者单次皮下注射0.2 U/kg剂量的赖脯胰岛素和常规胰岛素。每次给药前均过夜禁食，分别在腹部、三角肌或股部三个注射部位之一给药。研究药物在人工维持正常血糖的葡萄糖钳夹试验期间给予。在12小时的钳夹试验过程中采集血样，用于测量胰岛素反应成分，并从这些血清胰岛素和钳夹测量值中得出药代动力学和糖动力学测量结果。
无论注射部位如何，赖脯胰岛素与常规胰岛素的糖动力学比较显示，在更早的时间（TRmax）有更高的最大输注速率（Rmax）。赖脯胰岛素在各部位的总葡萄糖输注量（Gtot）显示出几乎相同的值。常规胰岛素在三角肌和股部注射后的Gtot值更高。当比较两种药物时，常规胰岛素产生的Gtot显著更高，主要是由于三角肌和股部注射的Gtot增加所致。无论注射部位如何，赖脯胰岛素在更早的时间（tmax）出现更高的最大血清胰岛素浓度（Cmax）（P<0.001）。腹部给药在最早的tmax时，常规胰岛素和赖脯胰岛素的Cmax值均最高。三角肌和股部注射的两种化合物的Cmax值较低。tmax也有变化，尽管常规胰岛素的这种变化比赖脯胰岛素大得多。两种化合物比较时，曲线下面积（AUC）值相当。
与腹部给药相比，三角肌和股部给药吸收较慢，导致常规胰岛素和赖脯胰岛素的作用持续时间延长。然而，只有常规胰岛素的起效时间有明显显著增加。腹部和肢体注射部位对赖脯胰岛素反应的一致性，使得皮下注射有更多潜在部位且能确保快速反应。
