Evaluation of the Pharmacokinetic Profile of Ultra Rapid Lispro Administered Subcutaneously at Different Injection Sites

• Published in: Clinical therapeutics 2022-06, Vol.44 (6), p.836-847
• Main Authors: Leohr, Jennifer K., Dellva, Mary Anne, LaBell, Elizabeth, Coutant, David E., Linnebjerg, Helle
• Format: Article
• Language: English
• Subjects: Abdomen; Bioavailability; Diabetes; Dosage; Drug delivery systems; Drug dosages; Euglycemic glucose clamp; Glucodynamics; Glucose; Injection; Injection site; Insulin; Insulin lispro; Insulin secretion; Intravenous administration; Laboratories; Pharmacokinetics; Pharmacology; Software; Thigh; Ultra rapid insulin; Vital signs
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/j.clinthera.2022.04.001

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