Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin

• Published in: Diabetes care Vol. 19; no. 12; pp. 1437 - 1440
• Main Authors: TER BRAAK, E. W, WOODWORTH, J. R, BIANCHI, R, CERIMELE, B, ERKELENS, D. W, THIJSSEN, J. H. H, KURTZ, D
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Diabetes Association 01.12.1996
• Subjects: Abdomen; Adult; Analysis of Variance; Arm; Biological and medical sciences; Blood Glucose - drug effects; Blood Glucose - metabolism; Cross-Over Studies; Glucose Clamp Technique; Hormones. Endocrine system; Humans; Injections, Subcutaneous; Insulin - administration & dosage; Insulin - analogs & derivatives; Insulin - pharmacokinetics; Insulin - pharmacology; Insulin Lispro; Leg; Male; Medical sciences; Pharmacology. Drug treatments; Random Allocation; Reference Values; Time Factors; Endocrinopathy; Human; Insulin lispro; Chemotherapy; Treatment; Insulin human; Diabetes mellitus; Injection site; Biological effect; Pharmacokinetics; Comparative study; Glycemia
• ISSN: 0149-5992; 1935-5548
• DOI: 10.2337/diacare.19.12.1437

Injection site effects on the pharmacokinetics and glucodynamics of insulin lispro and regular insulin. E W ter Braak , J R Woodworth , R Bianchi , B Cerimele , D W Erkelens , J H Thijssen and D Kurtz Lilly Laboratory for Clinical Research, Eli Lilly and Company, Wishard Memorial Hospital, Indianapolis, IN 46219, USA. Abstract OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.