医学
lispro胰岛素
药代动力学
餐后
胰岛素
交叉研究
丸(消化)
生物利用度
腹部
曲线下面积
起效
皮下注射
麻醉
内科学
内分泌学
外科
药理学
替代医学
病理
安慰剂
作者
Jennifer Leohr,Mary Anne Dellva,Elizabeth S. Labell,David E. Coutant,Helle Linnebjerg
标识
DOI:10.1016/j.clinthera.2022.04.001
摘要
PurposeUltra 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.MethodsIn 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.FindingsTotal 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.ImplicationsThe 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. ClinicalTrials.gov identifier: NCT03232983.
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