INJECTION SITE EFFECTS ON THE PHARMACOKINETICS AND GLUCODYNAMICS OF INSULIN LISPRO AND REGULAR INSULIN

OBJECTIVE - The pharmacokinetics and glucodynamics of a new insulin an alog, insulin lispro, and regular human insulin were compared and cont rasted after subcutaneous administrations in femoral, deltoid, and abd ominal injection sites. RESEARCH DESIGN AND METHODS - single 0.2 U/kg doses of insulin lispro and regular insulin were administered to 12 he althy subjects in a six-way randomized crossover fashion. Each dose wa s given after an overnight fast in one of three injection sites: abdom inal, deltoid, or femoral. Study drugs were given during a manual eugl ycemic 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 cla mp measurements. RESULTS - Glucodynamic comparisons between insulin li stro and regular insulin showed a greater maximum infusion rate (R(max )) at an earlier time (TR(max)), regardless of injection site. The tot al glucose infused (G(tot)) showed nearly identical Values between sit es for insulin lispro. Regular insulin showed greater G(tot). Values f rom deltoid and femoral injections. When comparisons were made between drugs, regular insulin produced significantly greater G(tot) primaril y 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 injec tion sire (P < 0.001). Abdominal administrations produced the greatest C-max values at the earliest t(max) for both regular insulin and insu lin lispro. Deltoid and femoral injections had lower C-max values for both compounds. Shifts also occurred with t(max), although these shift s were much greater with regular insulin than with insulin lispro. Equ ivalent area under the curve (AUC) values were found when compared bet ween compounds. CONCLUSIONS - Slower absorption from deltoid and femor al administrations resulted in an increased duration of action for bot h regular insulin and insulin lispro when compared to abdominal admini stration. However, notable increases in the onset of action were only apparent with regular insulin. The consistency with insulin lispro res ponse from abdominal and extremity injection sites allows more potenti al sites for subcutaneous injection with an assured rapid response.