Eli Lilly and Company, Indianapolis, IN, USA.
Eli Lilly and Company, Indianapolis, IN, USA.
Clin Ther. 2022 Jun;44(6):836-847. doi: 10.1016/j.clinthera.2022.04.001. Epub 2022 May 13.
Ultra rapid lispro (URLi) is a novel insulin lispro formulation developed to more closely match physiological insulin secretion and improve postprandial glucose control. This study compared the pharmacokinetic profile and glucodynamic response of URLi when administered subcutaneously into the abdomen, upper arm, or thigh. An intravenous (IV) bolus administration was included to determine the absolute bioavailability at each injection site.
In this Phase I, randomized, open-label, 4-period, crossover study, healthy subjects received a single dose of 15 U URLi subcutaneously into the abdomen, upper arm, or thigh, or by intravenous injection. Serum insulin lispro concentrations and glucodynamic response during a 10-hour euglycemic clamp procedure were assessed after URLi administration.
Total insulin lispro exposure was similar for the abdomen, upper arm, and thigh, and absolute bioavailability was ∼65% at each subcutaneous (SC) injection site. Total and peak insulin action were similar across these SC injection sites. The onset of appearance was <1 minute, and the time to early half-maximal drug concentration occurred at ∼10 minutes across these three SC injection sites. Onset of insulin action occurred at ∼22 minutes, and the early insulin action (for the first hour) was also similar across these SC injection sites. URLi was well tolerated after single SC injections and IV bolus administration.
The pharmacokinetic and glucodynamic profiles of URLi were similar after a single SC dose into the abdomen, upper arm, or thigh. The rate of insulin lispro absorption and early insulin action were maintained regardless of the SC injection site. The current study supports SC injection of URLi into the abdomen, upper arm, and thigh.
gov identifier: NCT03232983.
超快速赖脯胰岛素（URLi）是一种新型赖脯胰岛素制剂，旨在更接近生理胰岛素分泌，改善餐后血糖控制。本研究比较了 URLi 皮下注射于腹部、上臂或大腿时的药代动力学特征和血糖动力学反应。还进行了静脉内（IV）推注，以确定每个注射部位的绝对生物利用度。
这是一项 I 期、随机、开放标签、4 期交叉研究，健康受试者单次皮下注射 15 U URLi 至腹部、上臂或大腿，或静脉内注射。URLi 给药后，通过 10 小时的正葡萄糖钳夹程序评估血清胰岛素赖脯胰岛素浓度和血糖动力学反应。
腹部、上臂和大腿的总胰岛素赖脯胰岛素暴露相似，每个皮下（SC）注射部位的绝对生物利用度约为 65%。这些 SC 注射部位的总和峰值胰岛素作用相似。起效时间<1 分钟，早期半最大药物浓度时间在这些三个 SC 注射部位发生在约 10 分钟。胰岛素作用的起始时间发生在约 22 分钟，这些 SC 注射部位的早期胰岛素作用（前 1 小时）也相似。单次 SC 注射和 IV 推注后，URLi 耐受性良好。
单次 SC 剂量腹部、上臂或大腿注射后，URLi 的药代动力学和血糖动力学特征相似。无论 SC 注射部位如何，胰岛素赖脯胰岛素的吸收速度和早期胰岛素作用都得到维持。本研究支持将 URLi 皮下注射至腹部、上臂和大腿。
gov 标识符：NCT03232983。
