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

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 listro and regular insulin showed a greater maximum infusion rate (R(max)) at an earlier time (TR(max)), regardless of injection site. The total glucose infused (G(tot)) showed nearly identical Values between sites for insulin lispro. Regular insulin showed greater G(tot). Values from deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater G(tot) primarily driven by the increased G(tot) from deltoid and femoral injections. Greater maximum serum insulin concentrations (C-max) were experienced with insulin lispro at earlier times (t(max)), regardless of the injection sire (P < 0.001). Abdominal administrations produced the greatest C-max values at the earliest t(max) for both regular insulin and insulin lispro. Deltoid and femoral injections had lower C-max values for both compounds. Shifts also occurred with t(max), 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.