[Studies on the absorption kinetics of subcutaneously administered insulin]

Abstract

This study was designed to evaluate, using compartmental model analysis, the effects of jet injection, changes in injected dosage, and mixture of short- and intermediate-acting insulin preparations on the absorption kinetics of human insulin (HI) mainly in rabbits. The following results were obtained. (1) It was found that a split-pool model was adequate for the evaluation of the absorption kinetics of insulin. (2) Jet injection resulted in more rapid absorption of insulin than needle injection. Since parameter K12 (inter-pool rate constant) of jet injection was three times as large as that of needle injection, the accelerated absorption by jet injector could result from the rapid movement of insulin from the injection site to the absorption site. (3) A negative correlation between insulin dosage and Kd (degradation rate constant) was observed, suggesting that the process of subcutaneous absorption of insulin includes a nonlinear component. (4) The prompt injection of Actrapid HI mixed with Monotard HI in a single syringe caused a delayed absorption of Actrapid HI. In contrast, there was no prolonged absorption after the injection of regular HI mixed with NPH-HI in a single syringe. There was a significant positive correlation between the percent change of K12 (in separate injection and mixed injection) in vivo and the recovery rate of short-acting insulin when mixed with intermediate-acting insulin in vitro. In clinical studies of diabetic subjects, higher serum free insulin levels before noon and higher K12 values were observed after the mixed injection of regular HI and NPH-HI, compared with that of Actrapid HI and Monotard HI. These results suggest that the application of compartmental model analysis is useful to studying the absorption kinetics of subcutaneously injected insulin.